I obtained my Master in Biochemistry/Molecular Biology from Gomal University, D.I. khan, Master of Philosophy (MS) in Biochemistry/Molecular Biology from Quaid-I-Azam University, Pakistan, and a Ph.D. degree in Applied Life Sciences (Biochemistry/Molecular Biology) from the Division of Applied Life Science, Gyeongsang National University (GNU), South Korea. Following that, I completed a two Post-doctorate certificates at the Brain-Metabolic Neurodegenerative Disease Center, GNU, South Korea. Currently, I am serving as an Associate Professor and as a Head of the Institutional Research Board at Northwest Institute of Health Sciences (Khyber Medical University), Pakistan. Additionally, I am a member of the Central Institutional Review Board and Ethics Committee (Central IRB&EC). In collaboration with consultants and Clinical Researchers at Northwest General Hospital and Research Centre, I am engaged in writing clinical/Preclinical Research projects. My research focuses on the Biochemical/Molecular aspects of disease and clinical research related to Neurotrauma, Spinal Cord Injury, Stroke, Metabolic disorders and diabetes in human subjects. Furthermore, I am Good Clinical Practice (GCP) certified. I also got Health Professional Education certificate from Khyber Medical University, Peshawar, Pakistan.
Glial activation and neuroinflammation play significant roles in apoptosis as well as in the development of cognitive and memory deficits. Neuroinflammation is also a critical feature in the pathogenesis of neurodegenerative disorders such as Alzheimer and Parkinson's diseases. Previously, hesperetin has been shown to be an effective antioxidant and anti-inflammatory agent. In the present study, in vivo and in vitro analyses were performed to evaluate the neuroprotective effects of hesperetin in lipopolysaccharide (LPS)-induced neuroinflammation, oxidative stress, neuronal apoptosis and memory impairments. Based on our findings, LPS treatment resulted in microglial activation and astrocytosis and elevated the expression of inflammatory mediators such as phosphorylated-Nuclear factor-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the cortical and hippocampal regions and in BV2 cells. However, hesperetin cotreatment markedly reduced the expression of inflammatory cytokines by ameliorating Toll-like receptor-4 (TLR4)-mediated ionized calcium-binding adapter molecule 1/glial fibrillary acidic protein (Iba-1/GFAP) expression. Similarly, hesperetin attenuated LPS-induced generation of reactive oxygen species/lipid per oxidation (ROS/LPO) and improved the antioxidant protein level such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Haem-oxygenase (HO-1) in the mouse brain. Additionally, hesperetin ameliorated cytotoxicity and ROS/LPO induced by LPS in HT-22 cells. Moreover, hesperetin rescued LPS-induced neuronal apoptosis by reducing the expression of phosphorylated-c-Jun N-terminal kinases (p-JNK), B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), and Caspase-3 protein and promoting the Bcl-2 protein level. Furthermore, hesperetin enhanced synaptic integrity, cognition, and memory processes by enhancing the phosphorylated-cAMP response element binding protein (p-CREB), postsynaptic density protein-95 (PSD-95), and Syntaxin. Overall, our preclinical study suggests that hesperetin conferred neuroprotection by regulating the TLR4/NF-κB signaling pathway against the detrimental effects of LPS.
Chronic neuroinflammation is responsible for multiple neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Lipopolysaccharide (LPS) is an essential component of the gram-negative bacterial cell wall and acts as a potent stimulator of neuroinflammation that mediates neurodegeneration. Quercetin is a natural flavonoid that is abundantly found in fruits and vegetables and has been shown to possess multiple forms of desirable biological activity including anti-inflammatory and antioxidant properties. This study aimed to evaluate the neuroprotective effect of quercetin against the detrimental effects of LPS, such as neuroinflammation-mediated neurodegeneration and synaptic/memory dysfunction, in adult mice. LPS [0.25 mg/kg/day, intraperitoneally (I.P.) injections for 1 week]-induced glial activation causes the secretion of cytokines/chemokines and other inflammatory mediators, which further activate the mitochondrial apoptotic pathway and neuronal degeneration. Compared to LPS alone, quercetin (30 mg/kg/day, I.P.) for 2 weeks (1 week prior to the LPS and 1 week cotreated with LPS) significantly reduced activated gliosis and various inflammatory markers and prevented neuroinflammation in the cortex and hippocampus of adult mice. Furthermore, quercetin rescued the mitochondrial apoptotic pathway and neuronal degeneration by regulating Bax/Bcl2, and decreasing activated cytochrome c, caspase-3 activity and cleaving PARP-1 in the cortical and hippocampal regions of the mouse brain. The quercetin treatment significantly reversed the LPS-induced synaptic loss in the cortex and hippocampus of the adult mouse brain and improved the memory performance of the LPS-treated mice. In summary, our results demonstrate that natural flavonoids such as quercetin can be beneficial against LPS-induced neurotoxicity in adult mice.
Oxidative stress and energy imbalance strongly correlate in neurodegenerative diseases. Repeated concussion is becoming a serious public health issue with uncontrollable adverse effects in the human population, which involve cognitive dysfunction and even permanent disability. Here, we demonstrate that traumatic brain injury (TBI) evokes oxidative stress, disrupts brain energy homeostasis, and boosts neuroinflammation, which further contributes to neuronal degeneration and cognitive dysfunction in the mouse brain. We also demonstrate that melatonin (an anti-oxidant agent) treatment exerts neuroprotective effects, while overcoming oxidative stress and energy depletion and reducing neuroinflammation and neurodegeneration. Male C57BL/6N mice were used as a model for repetitive mild traumatic brain injury (rmTBI) and were treated with melatonin. Protein expressions were examined via Western blot analysis, immunofluorescence, and ELISA; meanwhile, behavior analysis was performed through a Morris water maze test, and Y-maze and beam-walking tests. We found elevated oxidative stress, depressed phospho-5′AMP-activated protein kinase (p-AMPK) and phospho- CAMP-response element-binding (p-CREB) levels, and elevated p-NF-κB in rmTBI mouse brains, while melatonin treatment significantly regulated p-AMPK, p-CREB, and p-NF-κB in the rmTBI mouse brain. Furthermore, rmTBI mouse brains showed a deregulated mitochondrial system, abnormal amyloidogenic pathway activation, and cognitive functions which were significantly regulated by melatonin treatment in the mice. These findings provide evidence, for the first time, that rmTBI induces brain energy imbalance and reduces neuronal cell survival, and that melatonin treatment overcomes energy depletion and protects against brain damage via the regulation of p-AMPK/p-CREB signaling pathways in the mouse brain.
Oxidative stress has been considered the main mediator in neurodegenerative disease and in normal aging processes. Several studies have reported that the accumulation of reactive oxygen species (ROS), elevated oxidative stress, and neuroinflammation result in cellular malfunction. These conditions lead to neuronal cell death in aging-related neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease. Chronic administration of d-galactose (d-gal) for a period of 10 weeks causes ROS generation and neuroinflammation, ultimately leading to cognitive impairment. In this study, we evaluated the estrogen receptor α (ERα)/silent mating type information regulation 2 homolog 1 (SIRT1)-dependent antioxidant efficacy of 17β-estradiol against d-gal-induced oxidative damage-mediated cognitive dysfunction in a male mouse model. The results indicate that 17β-estradiol, by stimulating ERα/SIRT1, halts d-gal-induced oxidative stress–mediated JNK/NF-ҡB overexpression, neuroinflammation and neuronal apoptosis. Moreover, 17β-estradiol ameliorated d-gal-induced AD-like pathophysiology, synaptic dysfunction and memory impairment in adult mouse brains. Interestingly, inhibition of SIRT1 with Ex527 (a potent and selective SIRT1 inhibitor) further enhanced d-gal-induced toxicity and abolished the beneficial effect of 17β-estradiol. Most importantly, for the first time, our molecular docking study reveals that 17β-estradiol allosterically increases the expression of SIRT1 and abolishes the inhibitory potential of d-ga. In summary, we can conclude that 17β-estradiol, in an ERα/SIRT1-dependent manner, abrogates d-gal-induced oxidative stress–mediated memory impairment, neuroinflammation, and neurodegeneration in adult mice.
The aim of the current study was to explore the underlying neuroprotective mechanisms of curcumin (50 mg/kg, for six weeks) against ethanol (5 mg/kg i.p., for six weeks) induced oxidative stress and inflammation-mediated cognitive dysfunction in mice. According to our findings, ethanol triggered reactive oxygen species (ROS), apoptosis, neuroinflammation, and memory impairment, which were significantly inhibited with the administration of curcumin, as assessed by ROS, lipid peroxidation (LPO), and Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/Heme-oxygenase-1) expression in the experimental mice brains. Moreover, curcumin regulated the expression of the glial cell markers in ethanol-treated mice brains, as analyzed by the relative expression TLR4 (Toll like Receptor 4), RAGE (Receptor for Advanced Glycations End products), GFAP (Glial fibrillary acidic protein), and Iba-1 (Ionized calcium binding adaptor molecule 1), through Western blot and confocal microscopic analysis. Moreover, our results showed that curcumin downregulated the expression of p-JNK (Phospo c-Jun N-Terminal Kinase), p-NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), and its downstream targets, as assessed by Western blot and confocal microscopic analysis. Finally, the expression of synaptic proteins and the behavioral results also supported the hypothesis that curcumin may inhibit memory dysfunction and behavioral alterations associated with ethanol intoxication. Altogether, to the best of our knowledge, we believe that curcumin may serve as a potential, promising, and cheaply available neuroprotective compound against ethanol-associated neurodegenerative diseases.
Glutamate-induced excitotoxicity, oxidative damage, and neuroinflammation are believed to play an important role in the development of a number of CNS disorders. We recently reported that a high dose of glutamate could induce AMPK-mediated neurodegeneration in the postnatal day 7 (PND7) rat brain. Yet, the mechanism of glutamate-induced oxidative stress and neuroinflammation in the postnatal brain is not well understood. Here, we report for the first time the mechanism of glutamate-induced oxidative damage, neuroinflammation, and neuroprotection by polyphenolic anthocyanins in PND7. PND7 rat brains, SH-SY5Y, and BV2 cells treated either alone with glutamate or in combination with anthocyanins and compound C were examined with Western blot and immunofluorescence techniques. Additionally, reactive oxygen species (ROS) assay and other ELISA kit assays were employed to know the therapeutic efficacy of anthocyanins against glutamate. A single injection of glutamate to developing rats significantly increased brain glutamate levels, activated and phosphorylated AMPK induction, and inhibited nuclear factor-E2-related factor 2 (Nrf2) after 2, 3, and 4 h in a time-dependent manner. In contrast, anthocyanin co-treatment significantly reduced glutamate-induced AMPK induction, ROS production, neuroinflammation, and neurodegeneration in the developing rat brain. Most importantly, anthocyanins increased glutathione (GSH and GSSG) levels and stimulated the endogenous antioxidant system, including Nrf2 and heme oxygenase-1 (HO-1), against glutamate-induced oxidative stress. Interestingly, blocking AMPK with compound C in young rats abolished glutamate-induced neurotoxicity. Similarly, all these experiments were replicated in SH-SY5Y cells by silencing AMPK with siRNA, which suggests that AMPK is the key mediator in glutamate-induced neurotoxicity. Here, we report for the first time that anthocyanins can potentially decrease glutamate-induced neurotoxicity in young rats. Our work demonstrates that glutamate is toxic to the developing rat brain and that anthocyanins can minimize the severity of glutamate-induced neurotoxicity in an AMPK-dependent manner.
Melatonin is a well-known potent endogenous antioxidant pharmacological agent with significant neuroprotective actions. Here in the current study, we explored the nuclear factor erythroid 2-related factor 2 (Nrf2) gene-dependent antioxidant mechanism underlying the neuroprotective effects of the acute melatonin against acute ethanol-induced elevated reactive oxygen species (ROS)-mediated neuroinflammation and neurodegeneration in the developing rodent brain. In vivo rat pups were co-treated with a single dose of acute ethanol (5 g/kg, subcutaneous (S.C.)) and a single dose of acute melatonin (20 mg/kg, intraperitoneal (I.P.)). Four hours after a single S.C. and I.P. injections, all of the rat pups were sacrificed for further biochemical (Western blotting, ROS- assay, LPO-assay, and immunohistochemical) analyses. In order to corroborate the in vivo results, we used the in vitro murine-hippocampal HT22 and microglial BV2 cells, which were subjected to knockdown with small interfering RNA (siRNA) of Nrf2 genes and exposed with melatonin (100 μM) and ethanol (100 mM) and proceed for further biochemical analyses. Our biochemical, immunohistochemical, and immunofluorescence results demonstrate that acute melatonin significantly upregulated the master endogenous antioxidant Nrf2 and heme oxygenase-1, consequently reversing the acute ethanol-induced elevated ROS and oxidative stress in the developing rodent brain, and in the murine-hippocampal HT22 and microglial BV2 cells. In addition, acute melatonin subsequently reduced the activated MAPK-p-P38-JNK pathways and attenuated neuroinflammation by decreasing the expression of activated gliosis and downregulated the p-NF-K-B/p-IKKβ pathway and decreased the expression levels of other inflammatory markers in the developing rodent brain and BV2 cells. Of note, melatonin acted through the Nrf2-dependent mechanism to attenuate neuronal apoptosis in the postnatal rodent brain and HT22 cells. Immunohistofluorescence results also showed that melatonin prevented ethanol-induced neurodegeneration in the developing rodent brain. The in vitro results indicated that melatonin induced neuroprotection via Nrf2-dependent manner and reduced ethanol-induced neurotoxicity. The pleiotropic and potent neuroprotective antioxidant characteristics of melatonin, together with our in vivo and in vitro findings, suppose that acute melatonin could be beneficial to prevent and combat the acute ethanol-induced neurotoxic effects, such as elevated ROS, neuroinflammation, and neurodegeneration in the developing rodent brain.
Phytomedicine based natural flavonoids have potent antioxidant, anti-inflammatory, and neuroprotective activities against neurodegenerative diseases. The aim of the present study is to investigate the potent neuroprotective and antioxidant potential effects of fisetin (natural flavonoid) against central nervous system (CNS)-insult, lipopolysaccharide (LPS)-induced reactive oxygen species (ROS), neuroinflammation, neurodegeneration, and synaptic/memory deficits in adult mice. The mice were injected intraperitoneally (i.p.) with LPS (250 μg/kg/day for 1 week) and a fisetin dosage regimen (20 mg/kg/day i.p. for 2 weeks, 1 week pre-treated to LPS and 1 week co-treated with LPS). Behavioral tests, and biochemical and immunofluorescence assays were applied. Our results revealed that fisetin markedly abrogated the LPS-induced elevated ROS/oxidative stress and activated phosphorylated c-JUN N-terminal Kinase (p-JNK) in the adult mouse hippocampus. Fisetin significantly alleviated LPS-induced activated gliosis. Moreover, fisetin treatment inhibited LPS-induced activation of the inflammatory Toll-like Receptors (TLR4)/cluster of differentiation 14 (CD14)/phospho-nuclear factor kappa (NF-κB) signaling and attenuated other inflammatory mediators (tumor necrosis factor-α (TNF-α), interleukin-1 β (IL1-β), and cyclooxygenase (COX-2). Furthermore, immunoblotting and immunohistochemical results revealed that fisetin significantly reversed LPS-induced apoptotic neurodegeneration. Fisetin improved the hippocampal-dependent synaptic and memory functions in LPS-treated adult mice. In summary, our results strongly recommend that fisetin, a natural potent antioxidant, and neuroprotective phytomedicine, represents a promising, valuable, and therapeutic candidate for the prevention and treatment of neurodegenerative diseases.
Abstract Background Recently, we and other researchers reported that brain metabolic disorders are implicated in Alzheimer’s disease (AD), a progressive, devastating and incurable neurodegenerative disease. Hence, novel therapeutic approaches are urgently needed to explore potential and novel therapeutic targets/agents for the treatment of AD. The neuronal adiponectin receptor 1 (AdipoR1) is an emerging potential target for intervention in metabolic-associated AD. We aimed to validate this hypothesis and explore in-depth the therapeutic effects of an osmotin-derived adiponectin-mimetic novel nonapeptide (Os-pep) on metabolic-associated AD. Methods We used an Os-pep dosage regimen (5 μg/g, i.p., on alternating days for 45 days) for APP/PS1 in amyloid β oligomer-injected, transgenic adiponectin knockout (Adipo−/−) and AdipoR1 knockdown mice. After behavioral studies, brain tissues were subjected to biochemical and immunohistochemical analyses. In separate cohorts of mice, electrophysiolocal and Golgi staining experiments were performed. To validate the in vivo studies, we used human APP Swedish (swe)/Indiana (ind)-overexpressing neuroblastoma SH-SY5Y cells, which were subjected to knockdown of AdipoR1 and APMK with siRNAs, treated with Os-pep and other conditions as per the mechanistic approach, and we proceeded to perform further biochemical analyses. Results Our in vitro and in vivo results show that Os-pep has good safety and neuroprotection profiles and crosses the blood-brain barrier. We found reduced levels of neuronal AdipoR1 in human AD brain tissue. Os-pep stimulates AdipoR1 and its downstream target, AMP-activated protein kinase (AMPK) signaling, in AD and Adipo−/− mice. Mechanistically, in all of the in vivo and in vitro studies, Os-pep rescued aberrant neuronal metabolism by reducing neuronal insulin resistance and activated downstream insulin signaling through regulation of AdipoR1/AMPK signaling to consequently improve the memory functions of the AD and Adipo−/− mice, which was associated with improved synaptic function and long-term potentiation via an AdipoR1-dependent mechanism. Conclusion Our findings show that Os-pep activates AdipoR1/AMPK signaling and regulates neuronal insulin resistance and insulin signaling, which subsequently rescues memory deficits in AD and adiponectin-deficient models. Taken together, the results indicate that Os-pep, as an adiponectin-mimetic novel nonapeptide, is a valuable and promising potential therapeutic candidate to treat aberrant brain metabolism associated with AD and other neurodegenerative diseases.
Traumatic brain injury (TBI) is a global risk factor that leads to long-term cognitive impairments. To date, the disease remains without effective therapeutics because of the multifactorial nature of the disease. Here, we demonstrated that activation of the c-Jun N-terminal kinase (JNK) is involved in multiple pathological features of TBI. Therefore, we investigated the disease-modifying therapeutic potential of JNK-specific inhibitor (SP600125) in TBI mice. Treating 2 different models of TBI mice with SP600125 for 7 days dramatically inhibited activated JNK, resulting in marked reductions of amyloid precursor protein (APP) expression level and in amyloid beta production and hyperphosphorylated tau and regulation of the abnormal expression of secretases. Furthermore, SP600125 strongly inhibited inflammatory responses, blood-brain barrier breakdown, apoptotic neurodegeneration, and synaptic protein loss, regulated prosurvival processes and improved motor function and behavioral outcomes in TBI mice. More interestingly, we found that SP600125 treatment ameliorated amyloidogenic APP processing and promoted the nonamyloidogenic pathway in TBI mouse brains. Our findings strongly suggest that active JNK is critically involved in disease development after TBI and that inhibition of JNK with SP600125 is highly efficient for slowing disease progression by reducing multiple pathological features in TBI mouse brains and regulating cognitive dysfunction.
Ethanol induces oxidative stress and its exposure during early developmental age causes neuronal cell death which leads to several neurological disorders. We previously reported that vitamin C can protect against ethanol-induced apoptotic cell death in the developing rat brain. Here, we extended our study to understand the therapeutic efficacy of vitamin C against ethanol-induced oxidative stress, neuroinflammation mediated neurodegeneration in postnatal day 7 (PND7) rat. A single episode of ethanol (5g/kg) subcutaneous administration to postnatal day 7 rat significantly induced the production of reactive oxygen species (ROS), and activated both microglia and astrocytes followed by the induction of different apoptotic markers. On the other hand, due to its free radical scavenging properties, vitamin C treatment significantly reduced the production of reactive oxygen species, suppressed both activated microglia and astrocytes and reversed other changes including elevated level of Bax/Bcl-2 ratio, cytochrome c and different caspases such as caspase-9 and caspase-3 induced by ethanol in developing rat brain. Moreover, vitamin C treatment also reduced ethanol-induced activation of Poly [ADP-Ribose] Polymerase 1(PARP-1) and neurodegeneration as evident from Flouro-Jade-B and Nissl stainined neuronal cell death in PND7 rat brain. These findings suggest that vitamin C mitigated ethanol-induced oxidative stress, neuroinflammation and apoptotic neuronal loss and may be beneficial against ethanol damaging effects in brain development.
Brain injury is a significant risk factor for chronic gliosis and neurodegenerative diseases. Currently, no treatment is available for neuroinflammation caused by the action of glial cells following brain injury. In this study, we investigated the quinpirole-mediated activation of dopamine D2 receptors (D2R) in a mouse model of traumatic brain injury (TBI). We also investigated the neuroprotective effects of quinpirole (a D2R agonist) against glial cell-induced neuroinflammation secondary to TBI in adult mice. After the brain injury, we injected quinpirole into the TBI mice at a dose of 1 mg/kg daily intraperitoneally for 7 days. Our results showed suppression of D2R expression and deregulation of downstream signaling molecules in ipsilateral cortex and striatum after TBI on day 7. Quinpirole administration regulated D2R expression and significantly reduced glial cell-induced neuroinflammation via the D2R/Akt/glycogen synthase kinase 3 beta (GSK3-β) signaling pathway after TBI. Quinpirole treatment concomitantly attenuated increase in glial cells, neuronal apoptosis, synaptic dysfunction, and regulated proteins associated with the blood–brain barrier, together with the recovery of lesion volume in the TBI mouse model. Additionally, our in vitro results confirmed that quinpirole reversed the microglial condition media complex-mediated deleterious effects and regulated D2R levels in HT22 cells. This study showed that quinpirole administration after TBI reduced secondary brain injury-induced glial cell activation and neuroinflammation via regulation of the D2R/Akt/GSK3-β signaling pathways. Our study suggests that quinpirole may be a safe therapeutic agent against TBI-induced neurodegeneration.
Brain injuries are a serious global health issue and are the leading cause of neurodegeneration. To date, there is no proper cure and treatment for brain-injury-induced neuropathological conditions because of a lack of sufficient knowledge and the failure to develop a drug due to the multi-pathological conditions in the brain. Herein, we explored the neurotherapeutic effects of Nicotinamide (NAM), against brain injury-induced neurodegeneration and behavioral problems. Treating injured mouse brains with NAM, for 7 days, significantly ameliorated several pathological events. Interestingly, NAM treatment significantly inhibited the injury-induced activation of receptor for advanced glycation end-products (RAGE), c-Jun N-terminal kinases (JNK), and neuroinflammatory mediators, such as NF-κB, TNF-α, IL-1β, and NOS2 in the brain, and it also regulated the levels of apoptotic markers, including Bax, caspase-3, and Bcl-2. Furthermore, treatment using NAM in TBI mice, significantly reversed synaptic protein loss and improved memory impairments and behavioral outcomes. Our findings suggested that NAM treatment reduced injury-induced secondary neurodegenerative pathology by modulating RAGE/JNK/NF-κB signaling in mice. Therefore, we recommend that NAM would be a safe and efficient therapeutic agent against brain-injury-induced neurodegeneration.
We aimed this study to determine the relationship of various factors related to poor immunization in children in an earthquake affected community.We conducted this cross-sectional study during 2007-2008 in Muzaffarabad district of Pakistani side of Kashmir. We selected 43 villages as clusters and in the second, 860 children between 12 and 24 months were selected from households through systematic sampling. Mothers of the eligible children were interviewed with a questionnaire. Logistic regression analysis was run to measure the association of various factors with appropriate immunization status of the children.We found that 74% of children had completed their required doses of routine immunization. There were greater odds of a child being unvaccinated if the family lived at a distance that was to be covered in more than 10 min by any transport (odds ratio [OR]: 1.12, confidence interval [CI]: 1.08-1.17), mother of the child was not educated (OR:2.4, 1.3-4.4), child belonged to a low socioeconomic status (OR:3.5, CI: 2.1-6.3), family had any challenge or situation that where they could not take the child to a health facility for vaccination (OR: 2.3, CI: 1.4-3.7) and for a female child that belonged to minority ethnic group (OR: 1.7, CI: 1.0-2.5).Improvement in access of communities, especially of minority and poor in disaster-stricken, to immunization services and female education and awareness about the need for immunization in children could play a role in improving immunization coverage in such settings.
Traumatic brain injury (TBI) is the major and leading cause of mortality and an alarming public health challenge. TBI leads to permanent cognitive, motor, sensory and psychotic disabilities. Patients suffering from the various and long-term repercussions of TBI currently have limited therapy choices. The current research work was designed to evaluate the beneficial and neuroprotective role of Troxerutin (Trox) (a natural flavonoid) in a closed brain injury mouse model. The male BALB/c 8-weeks old mice (n꞊150) were randomly distributed in three experimental groups. Control group of mice (n꞊50), TBI group (n꞊50) and Trox pre-treated mice group (Trox + TBI, n꞊50). The mice in Trox + TBI were pre-treated with Trox (150 mg/kg, 7 days) before TBI. The weight-drop mechanism was used to induce mild-moderate injury in mice in both the groups. Our results showed that the mice pre-treated with troxerutin significantly improved neurological severity score, blood glucose level, food intake and brain edema as compared to the mice in the TBI group. Furthermore, compared to the TBI group, the mice treated with troxerutin improved cognitive behavior as evaluated by Open field test, Shallow Water Maze and Y-Maze, decreased brain-infarct volume and blood-brain barrier (BBB) permeability, significantly decreased Reactive Oxygen Species (ROS), improved neuronal morphology and survival in the brain regions such as cortex and hippocampus. In summary, our data provided evidence that pre-treatment with troxerutin improved neurological functions, decreased the BBB permeability, improved behavior, reduced ROS and increased neuronal survival in the weight-drop close head traumatic injury mouse model.
Douepia tortuosa (D. tortuosa) has not been evaluated for its pharmacological significance prior to this.This study was aimed to identify bioactive compounds occurring in water (AQE), methanol (ME), ethyl acetate (EAE) and n-hexane (HE) extracts of D. tortuosa and to evaluate its antimicrobial and antioxidant potential.The microscopic analysis of the plant powder presented characteristic starch granules and calcium oxalate crystals.The ME presented the best extraction yield value campared to the other solvents.Maximum soluble phenolics content, 793.24 µg GAE/g was found in EAE.The extracts were screened out for the presence of bioactive compounds by using Fourier-Transform Infrared Spectroscopy (FT-IR) and Gas Chromatography-Mass Spectrometry (GC-MS).The FT-IR spectrum of various extracts indicated the dominancy of N-H, C-H, C=O, N-O and C-N functional groups.The GC-MS profiling indicated the presence of a spectrum of substantial medicinal compounds in various extracts including Squalene, Heptacosane, Cis-vaccenic acid, Octadecanoic acid, γ-Sitosterol, vitamin E, Tetracontane, Palmitoleic acid and Dotriacontane.The ME was highly effective antibacterial agent against K. pneumoniae whereas, EAE showed strong antibacterial activity against A. baumannii and E. coli.The EAE and AQE were the best antifungal agents against A. flavus and A. niger.According to IC50 values the AQE (32.422 µg/mL) and EAE (31.6895 µg/mL) has significantly comparable antioxidant activity with standard ascorbic acid (26.917 µg/mL).The plant can be explored in future for the isolation of antimicrobial, antioxidant and anticancer compounds with promising effects.
In developing countries bottle feeding has emerged a big public health problem while in developed countries the trend is opposite. Prevalence of breast feeding in Pakistan is 90-98% but in some subgroups of population it is as low as 60-80%. The objectives of the study were to determine the causes of non breast feeding in children less than six months of age in district Nowshera, and assess practice of starting first breast feeding to the newborn.A cross sectional study was conducted in ten union councils of district Nowshera. A total of 305 children under six month age were selected by simple random method. Data was collected on pre-designed questionnaire and analysed by descriptive statistics.The study included 198 children from rural and 107 from urban areas. Mothers/guardians of 71.8% children were uneducated. Causes of non breast feeding included perception of mothers of having insufficient milk (45.9%), working mothers (18.4%), mothers with chronic diseases (13.1%), children with congenital or acquired diseases (17%), mothers having next pregnancy (3.61%) whose mothers have been died (0.98 %) and twin babies (0.98%). On the other hand, 61% babies started breast feeding on first day, 19% on second, 10.8% on third and 3.9% after third day while 5.2% babies got no breast feeding at all.Main causes of non-breastfeeding in less than six month age are perception of having insufficient milk, working women and twin babies.
Editor,—Cat scratch disease (CSD) is a relatively common and self limited infection causing fever and lymphadenopathy mainly in children and adolescents.1Previously reported ocular complications of CSD include Parinaud’s oculoglandular conjunctivitis,2 papillitis,3neuroretinitis,4 peripapillary angiomatosis,5and serous neurosensory retinal detachment.6 We present a case of CSD associated with anterior uveitis, a scenario previously unreported. ### CASE REPORT A 51 year old man presented to us with a 2 week history of a painful, red left eye associated with a reduction in vision. He gave a clear account of being scratched by his kitten, over the left eyebrow 3 weeks earlier. The ensuing fever, rigors, and submandibular lymphadenopathy had led his general practitioners to prescribe a course of oral clarithromycin for presumed CSD. Our patient developed pain and redness of a moderate degree in …
<em>Background:</em> On 18 March 2020, the second case of COVID-19 in the capital territory was reported by the local health department of Islamabad who presented with typical COVID-19 symptoms and had travel history. As per directions of Chief FEDSD, a team of field epidemiologists conducted outbreak investigations. The main objectives of this study were to investigate the clinical and epidemiological patterns of disease transmission and implementation of recommended SOPs. <em>Methods:</em> Descriptive outbreak investigation followed by contact tracing was done in Kot Hathyal, Islamabad, from 21March to 4 April 2020. Each case was enrolled as per the WHO predefined case definition and questionnaire, and data was maintained in line list. The daily health status of affected individuals was monitored physically as well as through phone calls. Data was maintained in Microsoft Excel. Secondary attack rate, median age, male to female ratio and 95% confidence interval was calculated in OpenEpi (version 3.01) for low and high risk contact groups. <em>Results:</em> During investigation, 17 confirmed COVID-19 cases were enrolled as a result of contact with index case, male to female ratio was 5:1, and median age was 41 years (34 to 56 years). All cases exhibited symptoms compatible with COVID-19 except two. The median incubation period was 4 days. The secondary attack rate was 81.80%. No transmission from asymptomatic cases were noted. <em>Conclusion:</em> The index case was a foreign national who had arrived in Pakistan mid-November 2019 to attend a religious gathering at Lahore from 12 to 15 March 2020. The intra and inter city travel caused the introduction of 17 new cases in Islamabad. Due to the lack of fully-fledged isolation centers in Islamabad, a home-based isolation strategy was introduced for the first time in the country. As the affected area was densely populated, the whole area was cordoned off for two weeks. This was also the country's first lockdown.
Salinity is one of the major environmental threats which damages growth and productivity of the plants.Microbial assistance in such stressful environment is well recognized.Here in this study, we isolated indigenous microbes and investigated their rescuing potential in celery plants grown under salinity stress.Celery is a widely consumed plant in salads.Plants were cultivated under varying levels (5 & 10% in aqueous solution against control) of salinity in the greenhouse with inocula of two isolated strains of rhizobacteria (RB) which were screened from locally collected soil samples.Data (chlorophylls, carotenoids, anthocyanins, fresh and dry weights of plants, and lengths of root and shoot) were collected and analysed using SPSS.Biochemical isolation of the rhizobacteria was also performed.Plants inoculated with the isolated rhizobacterial strains indicated a statistically significant relief to the stressed plants which resulted in more chlorophylls' (a, b & total), carotenoid and anthocyanin contents that were at par with control.Post inoculation elongation of root and shoot as well as fresh and dry matter accumulations were enhanced significantly.RB 20 indicated statistically significant relief to the plants compared to RB 10.Bacterial strains screening results showed that strains RB 6 & RB 20 proved their positive relieving strengths in the tests of indole synthesis, siderophore production, phosphorus solubilization, casein hydrolysis, catalase activity, citrate biosynthesis, gelatinase biosynthesis, H2O2 production, motility test, osmotic regulation potential and starch hydrolysis.Hence, these indigenous microbes might be helpful in assisting celery plants grown under salinity conditions.
Traumatic brain injury (TBI) is a serious issue and a leading cause of death and disability worldwide. Caregivers of TBI patients experience psychological distress and a variety of social and financial issues. The present study aims to investigate the caregiver's burden and the factors that influence this burden. Furthermore, the present study will find out the association of religious practice, religious coping relations and psychological distress among caregivers of children affected with TBI.A cross-sectional survey was conducted on 302 caregivers of children with TBI using Duke University Religion Index (DURL) for religious practice. General Health Questionaire-12 (GHQ-12) was used for anxiety and depression and Brief Religious Coping Scale (RCOPE) was used for coping strategies. The caregivers were conveniently chosen from different regions of Khyber Pakhtunkhwa province and data was collected from different tertiary care hospitals in Peshawar.Forty-nine (49) % of caregivers score ≥ 3 on GHQ suffer from psychological distress with a Mean of 20.957 ± 4.175). Positive coping methods were mostly used by caregivers than negative coping have a low level of distress with a Mean Positive Coping (P-COPE ) of 6.93 ± 0.41, Mean of Negative Coping (N-COPE) 0.486 ± 1.023. In religious practice, caregivers mostly participate in Organized Reliogious Activities (ORA) or some Non-Organized Reliogious Activities (NORA) with a Mean ORA of 4.20 ± 1.27, and NORA Mean of 4.17 ± 1.37 used by the caregivers. Coping methods were related to Caregiver psychological distress (GHQ-12 and P-COPE co-relation scores are (ρ -0.022, p b 0.05); GHQ-12 scores and N-COPE (ρ + 0.221=, p b 0.001). There is a negative correlation between GHQ 12 and PCOPE, while GHQ12 is positively correlated with NCOPE.According to this study, there is a significant association between religious coping methods, religious practice, and psychological distress among caregivers of children with traumatic brain injury.
<title>Abstract</title> <bold>Background:</bold> Measles is a highly contagious viral disease that continues to pose a public health challenge, particularly in developing countries like Pakistan. Despite the availability of effective vaccines, measles outbreaks remain common, exacerbated by gaps in vaccination coverage and other socioeconomic factors. <bold>Objectives:</bold> This study aimed to determine the prevalence of measles and its association with vaccination status among children aged 4 months to 15 years presenting at Saidu Group of Teaching Hospital, Swat. <bold>Methodology:</bold> A cross-sectional study was conducted on 400 children diagnosed with measles. Data were collected using a structured questionnaire and analyzed with SPSS-27. Children were categorized into vaccinated and unvaccinated groups, and associations with demographic and clinical variables were assessed. <bold>Results:</bold> Among the 400 children, the prevalence of measles was 50.2%. The highest prevalence was observed in the 5–10 years age group (56.6%). A significant association was found between vaccination status and measles prevalence, with 43.34% of vaccinated and 67.4% of unvaccinated children affected (p = 0.04). Females had a significantly higher prevalence (58.65%) than males (p = 0.006). Complications occurred in 57.2% of cases, with pneumonia (37.4%) and diarrhea (27.8%) being the most frequent. <bold>Conclusion:</bold> The study highlights the effectiveness of measles vaccination in reducing disease incidence. However, cases among vaccinated children point to issues such as secondary vaccine failure and cold chain management. Enhanced immunization programs, improved healthcare access, and strategies to address vaccine hesitancy are critical to achieving measles elimination in Pakistan.
Background: Vaccination through the Expanded Program on Immunization (EPI) is one of the most cost-effective public health interventions, which has resulted in reduction in the morbidity and mortality from a number of vaccine preventable diseases. This study aimed to investigate up-to-date and age-appropriate EPI immunization coverage in two districts of Azad Jammu & Kashmir. Methods: A cross sectional survey was conducted between October, 2007 and December, 2007. A total of 420 children of 12-23 months were studied. The thirty clusters sampling technique by World Health Organization was used to collect the data. The “up-to-date” and “age appropriate” immunization coverage for the children was determined for both the districts. Pearson’s Chi-square test for categorical and T-test for continuous variables were used. Results: Overall 73.1% (CI=67.0-79.1%) of the children between 12-23 months had received “up-to-date” immunization in District Bagh. However, only 16.5 % (CI= 11.2-21.7%) were age-appropriately immunized. The dropout rates for DTP vaccine was 11.4% (CI=9.9-15.3%). For District Neelum, overall 60.5 % (CI=51.6-69.8%) children of 12-23 months had received “up-to-date” immunization. Only 33.3 % (CI=22.7%-44.0%) of children were age-appropriately immunized. The dropout rates for District Neelum for DTP vaccine was 28.2% (CI=21.3-35.7%). Conclusion: While up-to-date immunization coverage is above 60%, age appropriate immunization coverage is very low and almost less than 30% in Azad Jammu and Kashmir.
La question traitee dans cette etude aborde la qualite du service des bibliotheques universitaires du Pakistan a partir du point de vue de leurs usagers. Plus precisement, l'etude examine les perceptions, les attentes et la satisfaction des usagers quant a la qualite des services de la bibliotheque, l'ecart entre perceptions et attentes des usagers, les differences entre la qualite percue du service selon les usagers, leur sexe, la bibliotheque concernee et la discipline academique. Pour se faire, l'etude developpe une version Urdu du protocole LIBQUAL et en examine les proprietes psychometriques afin de valider le questionnaire dans le contexte pakistanais. A la connaissance de l'auteur, cette etude est la premiere tentative globale pour combler cette lacune en evaluant la qualite percue des services dans les bibliotheques universitaires du Pakistan grâce a LIBQUAL. Les donnees ont ete collectees a travers deux etudes distinctes par le biais d'un questionnaire papier adresse a des etudiants (premier cycle et au-dela) et a des personnels enseignants de 29 universites. 514 et 1473 questionnaires ont respectivement ete selectionnes de la premiere et de la seconde etude. L'analyse quantitative des donnees a ete realisee avec l'aide des logiciels Statistical Package for Social Sciences (SPSS) et l'Analyse des structures Moment (AMOS = Analysis of MOment Structures). Cette these fait une large part aux contributions et applications academiques pour l'etude presentee tout en considerant les limites. De nombreuses suggestions pour des recherches futures ont ete faites a la fin de cette etude.
Portal Hypertension can be due to many causes other than cirrhosis. We report a case of extra hepatic portal vein obstruction leading to portal hypertension and varices, managed successfully by creating a Porto Caval shunt.
Introduction: Testosterone administration increase rigidity and duration of erection in patients of erectile dysfunction. There is strong association of Erectile dysfunction with increasing age and decrease in the level of testosterone. The effects of deficiency of male hormones on sexual performance mainly by inhibiting the production or action of male hormones. Objective To find out prolactin in erectile dysfunction patients with/without Diabetes Mellitus and compare the difference in Testosterone levels of Erectile dysfunction patients across the two groups of diabetic and non-diabetic patients. Methodology A comparative cross-sectional study was conducted on 100 diabetics and 100 non-diabetic patients to assess Testosterone, both total and free was determined in patients of Erectile dysfunction with and without Diabetes Mellitus type-2. Calibrator measurements were also performed for testosterone. Independent sample t-test was performed for comparison between the two groups. Results Majority of patients were 40-49 years old (44.5%). Duration of Erectile Dysfunction was higher in Diabetic patients compared to Non-Diabetics. Free testosterone was significantly low in Diabetic group with a P value of 0.049. Conclusions There was no significant difference between the two groups in case of total testosterone.
ABSTRACT INTRODUCTION: Traumatic brain injury (TBI) is a major global health issue in both civilians and war-affected military personnel and has no proper cure or treatment. Survivors of TBI exhibit long-term cognitive dysfunction and even permanent disabilities. As TBI patients exhibit multiple pathological conditions and the exact mechanism of neuroinflammation and neurodegeneration is still remain elusive. Therefore, we assess the prolonged effects of penetrating brain injury in animal model to further explore the neuroinflammation-associated neuropathological conditions in clinical studies. OBJECTIVE: To determine the long term neuroinflammatory and neurodegenerative effects after penetrating brain injury in preclinical model. METHODOLOGY: In the present study, we developed a penetrating brain injury and examined compare the neuroinflammatory effects after seven days and two months following brain injury in animal model. We used confocal laser microscopy to assess the expression of neuroinflammatory mediators in the mice group. RESULTS: These findings provide evidence that penetrating brain injury have prolonged effects after two months. Using confocal laser microscopy, we found that the expression of GFAP (reactive astrocytes marker) and IL-1β (inflammatory marker) in the mice brain were significantly sustained after two months following brain injury, suggesting the prolonged neuroinflammatory effects after penetrating brain injury. Here, we found fascinating results that severity of neuroinflammation was higher at day 7 as compare to two months in animal brains. CONCLUSION: These findings provide evidence that penetrating brain injury is critically involved in prolonged neuroinflammation which effect the cognitive ability and neurological impairments in the brain. Furthermore, these findings would be supportive in the preclinical and clinical settings. KEY WORDS: inflammation, Traumatic brain injury, Astrocytes, interleukin beta.
Introduction: Prolactin is produced in man in several other tissues like brain, mammary gland, lymphocytes, spleen and thymus. The prolactin receptors are found mainly in the ovary and the mammary glands. Prolactin effects Erectile dysfunction in patients with and without Diabetes Mellitus type 2. Objective To find out prolactin in erectile dysfunction patients with/without Diabetes Mellitus and compare the difference in prolactin levels of Erectile dysfunction patients across the two groups of diabetic and non-diabetic patients. Methodology A comparative cross-sectional study was conducted on 100 diabetics and 100 non-diabetic patients to assess the effects of diabetes on erectile dysfunction. A convenience sampling technique was used to select patients from two hospitals. Calibrator measurements were also performed for prolactin. Independent sample t-test was performed for comparison between the two groups. Results Majority of patients were 40-49 years old (44.5%). Erectile dysfunction (ED) was significantly more common in older age groups. Duration of ED was higher in diabetic patients compared to non-diabetics. Prolactin level was higher in diabetics. Most diabetic and non-diabetic patients (48%) had mild severity of ED, however diabetic patients had slightly more severe form of ED compared to non-diabetics. Conclusions Erectile dysfunction is generally common in our setting. It may be associated with age and higher levels of prolactin. Moreover, Diabetic patients with erectile dysfunction have more significant deviation of these hormones as compared to their non-diabetic counterparts.
OBJECTIVE: To find-out the association of dyslipidemia with anxiety and depression in patients with polycystic ovarian syndrome (PCOS). METHODS: This descriptive cross-sectional study was conducted at Mardan Medical Complex, Mardan, Pakistan from December-2019 to March-2020. One hundred & forty diagnosed cases of PCOS, ranging in age from 20-40 years, were selected through purposive sampling. Anxiety and depression were calculated using hospital anxiety and depression scale (HADS) score. Total cholesterol (TC), triglycerides, low-density-lipoproteins (LDL), high-density-lipoproteins (HDL) and testosterone were tested through fasting blood samples. RESULTS: Anxiety and depression were documented in 102 (72.9%) & 99 (70.7%) cases respectively. Primary infertility, oligomenorrhoea, Hirsutism & acne were present in 69 (49.3%), 111 (73.5%), 81 (57.9%) and 55 (39.3%) patients respectively. Twenty-two (15.7%) patients were overweight/obese. All patients had raised testosterone levels and polycystic ovaries on ultrasound. Raised triglyceride levels (≥150 mg/dl), Low levels of HDL (≤ 60mg/dl), raised levels of LDL (≥130 mg/dl), raised cholesterol levels (≥200 mg/dl) were reported in 71/99 (71.7%), 56/99 (56.6%), 38/99 (38.4%) & 10/99 (10.2%) cases with depression as compared to 27/41 (65.9%), 13/41 (31.7%), 21/41 (51.2%) & 14/41(34.1%) non-depressed patients respectively. Similarly raised triglyceride levels, low levels of HDL, raised levels of LDL, raised cholesterol levels were reported in 73/102 (71.6%), 58/102 (56.9%), 40/102 (39.2%) & 12/102 (11.76%) cases with anxiety as compared to 25/38 (65.8%), 11/38 (28.9%), 19/38 (50%) and 12/38 (31.6%) patients without anxiety respectively. CONCLUSION: Dyslipidemia, anxiety and depression are very common in PCOS. Dyslipidemia is associated with anxiety and depression in PCOS patients.
Introduction:
 Prolactin is produced in man in several other tissues like brain, mammary gland, lymphocytes, spleen and thymus. The prolactin receptors are found mainly in the ovary and the mammary glands. Prolactin effects Erectile dysfunction in patients with and without Diabetes Mellitus type 2.
 
 Objective
 To find out prolactin in erectile dysfunction patients with/without Diabetes Mellitus and compare the difference in prolactin levels of Erectile dysfunction patients across the two groups of diabetic and non-diabetic patients.
 
 Methodology
 A comparative cross-sectional study was conducted on 100 diabetics and 100 non-diabetic patients to assess the effects of diabetes on erectile dysfunction. A convenience sampling technique was used to select patients from two hospitals. Calibrator measurements were also performed for prolactin. Independent sample t-test was performed for comparison between the two groups.
 
 Results
 Majority of patients were 40-49 years old (44.5%). Erectile dysfunction (ED) was significantly more common in older age groups. Duration of ED was higher in diabetic patients compared to non-diabetics. Prolactin level was higher in diabetics. Most diabetic and non-diabetic patients (48%) had mild severity of ED, however diabetic patients had slightly more severe form of ED compared to non-diabetics.
 
 Conclusions
 Erectile dysfunction is generally common in our setting. It may be associated with age and higher levels of prolactin. Moreover, Diabetic patients with erectile dysfunction have more significant deviation of these hormones as compared to their non-diabetic counterparts.
