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  1. Nathan FM, Ogawa S, Parhar IS
    J Neurochem, 2015 Nov;135(4):814-29.
    PMID: 26250886 DOI: 10.1111/jnc.13273
    The habenula, located on the dorsal thalamic surface, is an emotional and reward processing center. As in the mammalian brain, the zebrafish habenula is divided into dorsal (dHb) and ventral (vHb) subdivisions that project to the interpeduncular nucleus and median raphe (MR) respectively. Previously, we have shown that kisspeptin 1 (Kiss1) expressing in the vHb, regulates the serotonin (5-HT) system in the MR. However, the connectivity between the Kiss1 neurons and the 5-HT system remains unknown. To resolve this issue, we generated a specific antibody against zebrafish Kiss1 receptor (Kiss-R1); using this primary antibody we found intense immunohistochemical labeling in the ventro-anterior corner of the MR (vaMR) but not in 5-HT neurons, suggesting the potential involvement of interneurons in 5-HT modulation by Kiss1. Double-fluorescence labeling showed that the majority of habenular Kiss1 neurons are glutamatergic. In the MR region, Kiss1 fibers were mainly seen in close association with glutamatergic neurons and only scarcely within GABAergic and 5-HT neurons. Our findings indicate that the habenular Kiss1 neurons potentially modulate the 5-HT system primarily through glutamatergic neurotransmission via as yet uncharacterized interneurons. The neuropeptide kisspeptin (Kiss1) play a key role in vertebrate reproduction. We have previously shown modulatory role of habenular Kiss1 in the raphe serotonin (5-HT) systems. This study proposed that the habenular Kiss1 neurons modulate the 5-HT system primarily through glutamatergic neurotransmission, which provides an important insight for understanding of the modulation of 5-HT system by the habenula-raphe pathway.
  2. Nathan FM, Ogawa S, Parhar IS
    J Neurochem, 2015 Jun;133(6):870-8.
    PMID: 25818845 DOI: 10.1111/jnc.13105
    Kiss1, a neuropeptide predominantly expressed in the habenula, modulates the serotonin (5-HT) system to decrease odorant cue [alarm substance (AS)]-evoked fear behaviour in the zebrafish. The purpose of this study was to assess the interaction of Kiss1 with the 5-HT system as well as to determine the involvement of the 5-HT receptor subtypes in AS-evoked fear. We utilized 0. 28 mg/kg WAY 100635 (WAY), a selective 5-HT1A receptor antagonist, to observe the effects of Kiss1 administration on AS-evoked fear. We found WAY significantly inhibited the anxiolytic effects of Kiss1 (p < 0.001) with an exception of freezing behaviour. Based on this, we utilized 92.79 mg/kg methysergide, a 5-HT1 and 5-HT2 receptor antagonist, and found that methysergide significantly blocked the anxiolytic effects of Kiss1 in the presence of the AS (p < 0.001). From this, we conclude that Kiss1 modulates AS-evoked fear responses mediated by the 5-HT1A and 5-HT2 receptors. Kiss1 peptide intracranially (IC) administrated has been shown to decrease olfactory, alarm substance (AS)-evoked fear response. Blockade of the 5-HT1A receptor utilizing WAY 100635 (0.28 mg/kg) and the 5-HT1 and 5-HT2 receptor utilizing methysergide (92.79 mg/kg) produced increased AS-evoked fear responses that were unable to be overcome even during the recovery period. Blockade of this 5-HT system followed by Kiss1 administration showed that the peptide was unable to recover the anxiolytic effects upon 5-HT1A blocking using WAY 100635 with the exception of freezing behaviour while methysergide significantly blocked all the anxiolytic effects of Kiss1. These findings implicate that Kiss1 could modulate AS-evoked fear responses mediated by 5-HT1A and 5-HT2 receptors.
  3. Ogawa S, Nathan FM, Parhar IS
    Proc Natl Acad Sci U S A, 2014 Mar 11;111(10):3841-6.
    PMID: 24567386 DOI: 10.1073/pnas.1314184111
    Kisspeptin, a neuropeptide encoded by the KISS1/Kiss1, and its cognate G protein-coupled receptor, GPR54 (kisspeptin receptor, Kiss-R), are critical for the control of reproduction in vertebrates. We have previously identified two kisspeptin genes (kiss1 and kiss2) in the zebrafish, of which kiss1 neurons are located in the habenula, which project to the median raphe. kiss2 neurons are located in the hypothalamic nucleus and send axonal projections to gonadotropin-releasing hormone neurons and regulate reproductive functions. However, the physiological significance of the Kiss1 expressed in the habenula remains unknown. Here we demonstrate the role of habenular Kiss1 in alarm substance (AS)-induced fear response in the zebrafish. We found that AS-evoked fear experience significantly reduces kiss1 and serotonin-related genes (plasmacytoma expressed transcript 1 and solute carrier family 6, member 4) in the zebrafish. Furthermore, Kiss1 administration suppressed the AS-evoked fear response. To further evaluate the role of Kiss1 in fear response, zebrafish Kiss1 peptide was conjugated to saporin (SAP) to selectively inactivate Kiss-R1-expressing neurons. The Kiss1-SAP injection significantly reduced Kiss1 immunoreactivity and c-fos mRNA in the habenula and the raphe compared with control. Furthermore, 3 d after Kiss1-SAP injection, the fish had a significantly reduced AS-evoked fear response. These findings provide an insight into the role of the habenular kisspeptin system in inhibiting fear.
  4. Nathan FM, Singh VA, Dhanoa A, Palanisamy UD
    BMC Cancer, 2011;11:382.
    PMID: 21871117 DOI: 10.1186/1471-2407-11-382
    Oxidative stress is characterised by an increased level of reactive oxygen species (ROS) that disrupts the intracellular reduction-oxidation (redox) balance and has been implicated in various diseases including cancer. Malignant tumors of connective tissue or sarcomas account for approximately 1% of all cancer diagnoses in adults and around 15% of paediatric malignancies per annum. There exists no information on the alterations of oxidant/antioxidant status of sarcoma patients in literature. This study was aimed to determine the levels of oxidative stress and antioxidant defence in patients with primary bone and soft tissue sarcoma and to investigate if there exists any significant differences in these levels between both the sarcomas.
  5. Ilyas U, Butt A, Awan K, Asim J, Shakoor MS, Fatima M
    Malays J Med Sci, 2024 Aug;31(4):218-222.
    PMID: 39247103 DOI: 10.21315/mjms2024.31.4.18
    Adolescence is a transitional stage between puberty and maturity. Significant alterations in brain chemistry and hormone activity cause mood swings and other psychological and physical symptoms. On their journey to adolescence, adolescents deal with complex emotions, moral dilemmas, sexual concerns, identity crises and particular societal expectations related to their upbringing. Impulsivity in adolescents is frequent and causes multiple issues. Impulsivity often lead towards non-suicidal self-injury (NSSI), which has devastating consequences, which are both physical and mental. Both impulsivity and NSSI have their roots in brain chemistry and its related functions. The aim of this special communication was to delve into brain chemistry through studying the function of neurotransmitters and brain areas in NSSI and impulsivity. Multiple papers were sought on the topic of neurochemistry and neuroanatomy. The results identified serotonin, dopamine and glutamate as the neurotransmitters responsible for NSSI and impulsivity. Dysregulation in these neurotransmitters lead to the presentation of NSSI and impulsivity. Other than the neurotransmitters, the brain areas identified were prefrontal cortex, medial prefrontal cortex and ventrolateral prefrontal cortex. The compiled results of this research would help individuals in understanding the neurotransmitters and the brain areas responsible. This would also help in generating awareness regarding the biological nature of the phenomenon as well, leading to less stigmatisation. The less stigmatisation towards these phenomena can help the affected individuals to seek help without any guilt or shame, along with support from society as well.
  6. Saleem Z, Hassali MA, Godman B, Fatima M, Ahmad Z, Sajid A, et al.
    PMID: 32774870 DOI: 10.1186/s40545-020-00233-3
    Introduction: Resistant strains of bacteria are rapidly emerging with increasing inappropriate use of antibiotics rendering them less efficacious. Self-purchasing of antibiotics particularly for viral infections is a key driver of inappropriate use, especially in lower- and middle-income countries. There is a particular issue in countries such as Pakistan. Consequently, there is a need to assess current rates of self-purchasing especially for reserve antibiotics to guide future policies.

    Aims: Assess the extent of current antibiotic sales without a prescription in urban areas of Pakistan.

    Methodology: A multicenter cross-sectional study was conducted in different areas of Punjab, Pakistan using Simulated Client technique. The investigators demanded different predefined antibiotics from WHO AWaRe groups without prescription. Three levels of demand were used to convince the pharmacy staff in order to dispense the antibiotic without a prescription. A data collection form was completed by simulated clients within 15 min of each visit.

    Results: Overall 353 pharmacies and medical stores were visited out of which 96.9% pharmacies and medical stores dispensed antibiotics without demanding a prescription (82.7% at demand level 1 and 14.2% at demand level 2), with only 3.1% of pharmacies refusing to dispense antibiotics. The most frequently dispensed antibiotic was ciprofloxacin (22.1%). Surprisingly, even the reserve group antibiotics were also dispensed without a prescription. In only 25.2% visits, pharmacy staff guided patients about the use of antibiotics, and in only 11.0% pharmacists enquired about other medication history.

    Conclusion: Currently, antibiotics are easily acquired without a legitimate prescription in Pakistan. There is a need for strict adherence to regulations combined with a multi-dimensional approach to enhance appropriate dispensing of antibiotics and limit any dispensing of WHO restricted antibiotics without a prescription.

  7. Naqvi AA, Hassali MA, Naqvi SBS, Shakeel S, Zia M, Fatima M, et al.
    BMC Musculoskelet Disord, 2020 Feb 01;21(1):65.
    PMID: 32007095 DOI: 10.1186/s12891-020-3078-y
    BACKGROUND: Non-adherence to physical therapy ranges from 14 to 70%. This could adversely affect physical functioning and requires careful monitoring. Studies that describe designing and validation of adherence measuring scales are scant. There is a growing need to formulate adherence measures for this population. The aim was to develop and validate a novel tool named as the General Rehabilitation Adherence Scale (GRAS) to measure adherence to physical therapy treatment in Pakistani patients attending rehabilitation clinics for musculoskeletal disorders.

    METHODS: A month-long study was conducted in patients attending physical therapy sessions at clinics in two tertiary care hospitals in Karachi, Pakistan. It was done using block randomization technique. Sample size was calculated based on item-to-respondent ratio of 1:20. The GRAS was developed and validated using content validity, factor analyses, known group validity, and sensitivity analysis. Receiver operator curve analysis was used to determine cut-off value. Reliability and internal consistency were measured using test-retest method. Data was analyzed through IBM SPSS version 23. The study was ethically approved (IRB-NOV:15).

    RESULTS: A total of 300 responses were gathered. The response rate was 92%. The final version of GRAS contained 8 items and had a content validity index of 0.89. Sampling adequacy was satisfactory, (KMO 0.7, Bartlett's test p-value 0.95 while absolute fit index of root mean square of error of approximation was

  8. Sristi, Fatima M, Sheikh A, Almalki WH, Talegaonkar S, Dubey SK, et al.
    J Drug Target, 2023 Jun;31(5):486-499.
    PMID: 37125741 DOI: 10.1080/1061186X.2023.2205609
    With the advancement of nanotechnology, many different forms of nanoparticles (NPs) are created, which specifically enhance anticancer drug delivery to tumour cells. Albumin bio-macromolecule is a flexible protein carrier for the delivery of drugs that is biodegradable, biocompatible, and non-toxic. As a result, it presents itself as an ideal material for developing nanoparticles for anticancer drug delivery. Toxicological investigations demonstrated that this novel drug delivery technique is safe for use in the human population. Furthermore, drug compatibility with the albumin nanoparticle is remarkable. The robust structure of the nanoparticle, high drug encapsulation, and customisable drug release make it a promising carrier option for the treatment of lung cancer. In this review, we summarise human serum albumin and bovine serum albumin in the targeted delivery of anticancer drugs to lung cancer cells.
  9. Abbas SA, Khan A, Fatima M, Kalusalingam A, Kanakal MM, Inamdar SK, et al.
    PMID: 38357954 DOI: 10.2174/0118715230285370240131111539
    BACKGROUND: Seeds of plant Scaphium affine are traditionally used by the healers of "India" for the treatment of piles.

    OBJECTIVES: The primary objective of the study was to assess the anti-hemorrhoidal potential of the ethanolic seed extract of Scaphium affine.

    METHODS: After the soxhlet extraction method, the seed extract from Scaphium affine was first submitted to phytochemical standardization and then GC-MS analysis. Rats were given Croton oil and Jatropha oil to develop hemorrhoids, and Scaphium affine seed extract (ESA) was administered orally for 5 days and 3 days, respectively, at doses of 1000 and 500 mg/kg. The Rectoanal coefficient (RAC) was calculated as an inflammatory marker. The hemorrhoidal tissues were also subjected to cytokine profiling, biochemical estimation and histopathology.

    RESULTS: ESA demonstrated the presence of flavonoids, saponins, phytosterols, phenols, and tannins. GCMS analysis elucidated the presence of hexadecanoic acid 2 hydroxy -1,3 propane diyl ester,9 Octadecanoic acid ethyl ester, Cyclohexane 1,4 di methyl cis, Farnesol isomer,1, E-11, Z-13 octa decatriene, Stigmasterol, N-(5 ethyl -1,3,4-thiadiazol-yl) benzamide, N, N Dinitro 1,3,5,7 tetraza bicyclo 93,3,1) as major phytoconstituents. The results depicted more potent anti-hemorrhoidal activity of ESA at 1000 mg/kg, p.o., which was evident through a decrease in RAC. A significant decline in the levels of IL-1β, IL-6, and TNF-α expression was observed, along with the restoration of altered antioxidants and enzymes. Histopathological analysis confirmed the tissue recovery as it revealed minimal inflammation and decreased dilated blood vessels in treated animals.

    CONCLUSION: Based on the results it can be concluded that seeds of Scaphium affine showed significant anti-hemorrhoid agents which may be attributed to their anti-inflammatory and anti-oxidant potential due to the presence of certain phytoconstituents in it. The study also supports the traditional use of seeds of Scaphium affine for the first time in the treatment of hemorrhoids.

  10. Naqvi AA, Hassali MA, Iffat W, Zia M, Fatima M, Shakeel S, et al.
    Int J Rheum Dis, 2019 Nov;22(11):2031-2044.
    PMID: 31595667 DOI: 10.1111/1756-185X.13721
    AIM: Rheumatoid arthritis (RA) is a chronic progressive disabling disease that mainly affects joints. Studies documenting Pakistani patients' knowledge regarding RA disease are lacking and there is a need for such endeavor. The purpose of this study was to develop and validate a novel research tool to document patient knowledge about RA disease.

    METHODS: A novel research instrument known as the rheumatoid arthritis knowledge assessment scale (RAKAS) which consisted of 13 items, was formulated by a rheumatology panel and used for this study. This study was conducted in rheumatology clinics of three tertiary care hospitals in Karachi, Pakistan. The study was conducted in March-April 2018. Patients were recruited using a randomized computer-generated list of appointments. Sample size was calculated based on item-to-respondent ratio of 1:15. The validities, factor structure, sensitivity, reliability and internal consistency of RAKAS were assessed. The study was approved by the institutional Ethics Committee.

    RESULTS: A total of 263 patients responded to the study. Content validity was 0.93 and response rate was 89.6%. Factor analysis revealed a 3-factor structure. Fit indices, namely normed fit index (NFI), Tucker Lewis index (TLI), comparative fit index (CFI) and root mean square of error approximation (RMSEA) were calculated with satisfactory results, that is, NFI, TLI and CFI > 0.9, and RMSEA 19 and difficulty index <0.95. Sensitivity and specificity of RAKAS were above 90%. The tool established construct and known group validities.

    CONCLUSION: A novel tool to document disease knowledge in patients with RA was formulated and validated.

  11. Naqvi AA, Hassali MA, Iffat W, Shakeel S, Zia M, Fatima M, et al.
    Int J Rheum Dis, 2020 Jul;23(7):918-927.
    PMID: 32525287 DOI: 10.1111/1756-185X.13860
    AIM: To carry out cross-culture adaptation and validation of the English version of Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS) in patients with rheumatoid arthritis (RA).

    METHODS: A cross-sectional study was conducted for 2 months in 2 tertiary care hospitals in Karachi, Pakistan. Sample size was calculated based on item-subject ratio. The translation was carried out using standard procedures for translation and cross-culture adaptation. The validation process included estimation of discrimination power, item difficulty index, factorial, convergent, construct and known group validities and reliability. Reliability of the scale was estimated using Kuder-Richardson Formula 20 and a value of σ2  ≥ 0.6 was acceptable. SPSS v23, Remark Classic OMR v6 software and MedCalc Statistical Software v16.4.3, were used to analyze the data. The study was approved by the relevant ethics committee (IRB#NOV:15).

    RESULTS: The mean score was 7.68 ± 2.52 (95% CI: 7.31-8.05) for 177 patients. The σ2  = 0.601, that is, >0.6, test-retest reliability ρ = .753, P 

  12. Alhassan HH, Al-Keridis LA, Ayub H, Alenazy FO, Alruwaili Y, Khan MR, et al.
    Heliyon, 2023 Aug;9(8):e19324.
    PMID: 37664756 DOI: 10.1016/j.heliyon.2023.e19324
    Fruit of Carissa opaca Stapf ex Haines (C. opaca) is a feed additive and is commonly used against cardiac dysfunction, fever, asthma, diarrhea, gastrointestinal ailments, and skin diseases. In this study, we aimed to evaluate the metabolic profile and antioxidant potential of C. opaca fruit against carbon tetrachloride (CCl4)-induced cardiotoxicity and testicular toxicity in rats. Gas Chromatoghraphy-Mass Spectrometry (GC-MS) analysis of C. opaca fruit for the identification of potential metabolic profile, followed by methanolic extract of C. opaca and its derived fractions including n-hexane, ethyl acetate, chloroform, butanol, and aqueous were used to assess the antioxidant potential of fruits. Ten groups of rats received different treatments and got evaluated for cardiac and testicular antioxidant enzymes, histological architecture, and serum hormonal levels. GC-MS analysis of methanolic extract of C. opaca fruit showed the presence of some bioactive metabolites like cyclodecane, diethyl 2,6-pyridine dicarboxylate, tetrahydro-geraniol, S-[2-[N, N-Dimethylamino]ethyl]morpoline, 2,3-Methylenedioxyphenol, alpha-d-Glucopyranoside, 5,10-Diethoxy-2,3,7,8-tetrahydro-1H, 6H-dipyrrolo [1,2-a; 1',2'-d] pyrazine and 1,3-Benzothiazol-2(3H)-one,3-(3,3-dimethyl-1-oxobutyl) that corresponds the medicinal properties of C. opaca fruit. Prepared fractions of C. opaca fruits mitigated the toxicity induced by CCl4 in the heart and testicular tissues of rats. Oxidative stress was caused by the inhibition of activities of glutathione and other antioxidant enzymes of the body, while on the other hand elevating the levels of nitrite and hydrogen peroxide. Treatment with C. opaca fruit extract normalized the levels of enzymes, reproductive hormones, and free radicals thus restoring the histopathological and enzymatic biomarkers towards the normal group. The study supports the indigenous use of fruits as an alternative medicine against cardiac dysfunction by providing scientific evidence of protection against CCl4-induced injuries, and it also concludes the antioxidant defensive role in testicular tissues.
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