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The current study explored the effects of natural compounds, berbamine, bergapten, and carveol on paclitaxel-associated neuroinflammatory pain. Berbamine, an alkaloid obtained from BerberisamurensisRuprhas been previously researched for anticancer and anti-inflammatory potential. Bergapten is 5-methoxsalenpsoralen previously investigated in cancer, vitiligo, and psoriasis. Carveol obtained from caraway is a component of essential oil. The neuropathic pain model was induced by administering 2 mg/kg of paclitaxel (PTX) every other day for a week. After the final PTX injection, a behavioral analysis was conducted, and subsequently, tissue was collected for molecular analysis. Berbamine, bergapten, and carveol treatment attenuated thermal hypersensitivity, improved latency of falling, normalized the changes in body weight, and increased the threshold for pain sensation. The drugs increased the protective glutathione (GSH) and glutathione S-transferase (GST) levels in the sciatic nerve and spinal cord while lowering inducible nitric oxide synthase (iNOS) and lipid peroxidase (LPO). Hematoxylin and eosin (H and E) and immunohistochemistry (IHC) examinations confirmed that the medication reversed the abnormal alterations. The aforementioned natural substances inhibited cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κb) overexpression, as evidenced by enzyme-linked immunosorbant assay (ELISA) and Western blot and hence provide neuroprotection in chronic constriction damage.

This present study aimed to delineate Rumex hastatus D. Don crude extract (Rh.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rh.n-Hex, Rh.ETAC, Rh.Aq) and rutin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti H. pylori, antiulcer effects, and toxicology. The preliminary phytochemical analysis of Rumex hastatus showed different phytoconstituents and shows different peaks in GC-MC chromatogram. Rumex hastatus crude extract (Rh.Cr), fractions, and rutin attributed dose-dependent (50–300 mg/kg) protection (0–100%) against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance traversed by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, Rh.Cr and Rh.ETAC caused a concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contractions at a similar concentration range, whereas Rh.n-Hex, rutin, and verapamil were relatively potent against K+-induced contractions and shifted the Ca2+ concentration–response curves (CRCs) to the right, Rh.Cr (0.3–1 mg/mL) and Rh.ETAC (0.1–0.3 mg/mL) shifted the isoprenaline-induced inhibitory CRCs to the left. Rh.n-Hex, Rh.ETAC and rutin showed anti-H. pylori effect, also shows an inhibitory effect against H+/K+-ATPase. Rumex hastatus showed gastroprotective and antioxidant effects. Histopathological evaluation showed improvement in cellular architecture and a decrease in the expression of inflammatory markers such as, cyclooxygenase (COX-2), tumor necrosis factor (TN,F-α) and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry and ELISA techniques. In RT-PCR it decreases H+/K+-ATPase mRNA levels. Rumex hastatus was found to be safe to consume up to a dose of 2000 mg/kg in a comprehensive toxicity profile. Docking studies revealed that rutin against H+/K+-ATPase pump and voltage-gated L-type calcium channel showed E-values of −8.7 and −9.4 Kcal/mol, respectively. MD simulations Molecular Mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area (MMPBSA/GBSA) findings are consistent with the in-vitro, in-vivo and docking results.

•Polio is considered a serious threat to public health in Pakistan.•Online commenters show empathy for polio health care workers.•Misinformation on polio vaccine as an amplification of new polio cases.•Online commenters correct misinformation and false claims by providing factual information on polio.•Pakistan launches the Perception Management Initiative (PMI) to block anti-vaccination propaganda social media pages. Polio, which is caused by poliovirus, is a contagious, potentially crippling, and deadly disease. Pakistan is one of the countries in which polio is still endemic in the 21st century. In 2019, 146 polio cases were reported across the country with some resulting in deaths. Following the spread of rumors insinuating that children were falling sick after receiving an anti-polio vaccine, a mob attacked and set fire to a small hospital in the Peshawar district in April 2019. The present study investigates readers’ discussions that emerged from Dawn’s online readers’ comments on polio-related news stories in Pakistan. Using thematic analysis, we analyzed (N = 2216) comments made by readers in the polio-related news stories published on Dawn.com from January 1, 2012, to March 1, 2020. Seven major themes emerged from the analysis of the comments: 1) reasons for and challenges resulting in the failure to eradicate polio; 2) proposed solutions and policy changes to eradicate polio; 3) misinformation; 4) criticism, frustration, and shame; 5) comparison of Pakistan to other countries; 6) the internet as a public sphere; 7) suffering, empathy, and appreciation. Overall, our findings suggested that commenters are knowledgeable about polio vaccines and consider polio a serious threat to public health in Pakistan. Our study not only validated previous study findings such as reasons, challenges, and issues related to polio vaccination, but also found new challenges in online news sites concerning misinformation on polio and polio vaccination in Pakistan.

Pakistan is one of only three poliomyelitis-endemic countries in the world. Twelve wild poliovirus (WPV) cases were recorded in the country in 2018. Even though resistance to oral polio vaccine (OPV) has decreased over time, there are still pockets of communities, mostly ethnic Pakhtun living in the Khyber Pakhtunkhwa (KP) province, that resist OPV. Although local journalists may be important sources of health information, past studies have overlooked their role in this context. The purpose of this study was to examine Pakhtun health journalists’ beliefs regarding OPV and their views of the barriers and facilitators that influence OPV acceptance or hesitancy in their communities. We recruited and interviewed 33 Pakhtun journalists covering health issues for diverse media outlets in high-risk districts for WPV of the KP province. The semi-structured interviews were translated, transcribed, and analyzed for themes. The participants strongly supported OPV and advocated that children in their own families and communities get vaccinated against polio. At the same time, they felt that their communities faced more urgent health needs that were not addressed by the government. They identified barriers at the media organizational level operating against accurate coverage of OPV, including financial and time constraints, a lack of checks and balances, and limited health literacy. They regarded press releases issued by the officials associated with OPV campaigns as the main facilitators in the coverage of OPV. The participants perceived lack of community trust in the government, security concerns, and community members’ religious beliefs as the major impediments to increase in uptake of OPV. Pakhtun health journalists have the potential to be important partners in national polio eradication initiatives. They should receive culturally sensitive training in local languages at appropriate literacy levels. We also suggest direct involvement of journalists in community mobilization efforts.

Background Selective serotonin reuptaker inhibitors, including fluoxetine, are widely studied and prescribed antidepressants, while their exact molecular and cellular mechanism are yet to be defined. We investigated the involvement of HDAC1 and eEF2 in the antidepressant mechanisms of fluoxetine using a lipopolysaccharide (LPS)-induced depression-like behavior model. Methods For in vivo analysis, mice were treated with LPS (2 mg/kg BW), fluoxetine (20 mg/kg BW), HDAC1 activator (Exifone: 54 mg/kg BW) and NH125 (1 mg/kg BW). Depressive-like behaviors were confirmed via behavior tests including OFT, FST, SPT, and TST. Cytokines were measured by ELISA while Iba-1 and GFAP expression were determined by immunofluorescence. Further, the desired gene expression was measured by immunoblotting. For in vitro analysis, BV2 cell lines were cultured; treated with LPS, exifone, and fluoxetine; collected; and analyzed. Results Mice treated with LPS displayed depression-like behaviors, pronounced neuroinflammation, increased HDAC1 expression, and reduced eEF2 activity, as accompanied by altered synaptogenic factors including BDNF, SNAP25, and PSD95. Fluoxetine treatment exhibited antidepressant effects and ameliorated the molecular changes induced by LPS. Exifone, a selective HDAC1 activator, reversed the antidepressant and anti-inflammatory effects of fluoxetine both in vivo and in vitro, supporting a causing role of HDAC1 in neuroinflammation allied depression. Further molecular mechanisms underlying HDAC1 were explored with NH125, an eEF2K inhibitor, whose treatment reduced immobility time, altered pro-inflammatory cytokines, and NLRP3 expression. Moreover, NH125 treatment enhanced eEF2 and GSK3β activities, BDNF, SNAP25, and PSD95 expression, but had no effects on HDAC1. Conclusions Our results showed that the antidepressant effects of fluoxetine may involve HDAC1-eEF2 related neuroinflammation and synaptogenesis.

PurposeNurses' turnover intention has become a major issue in developing countries with high power distance cultures. Therefore, the authors attempt to investigate how turnover intention among nurses' can be reduced through paternalistic leadership (PL). The authors further investigate the mediating role of job satisfaction between the associations of benevolent, moral and authoritarian dimensions of PL with turnover intention. Finally, the authors examined perceived organizational support (POS) as a conditional variable between job satisfaction and turnover intention.Design/methodology/approachThe authors collected data from 374 nurses working in public and private hospitals of high power distance culture using a questionnaire-based survey on convenience basis.FindingsStructural equation modeling confirms that benevolent and moral dimensions of PL positively affect nurses' job satisfaction which helps them reduce their turnover intention. While the authoritarian dimension of PL negatively affects job satisfaction to further enhance their turnover intention. In addition, the authors noted POS as a conditional variable to trigger the negative effect of job satisfaction on turnover intention.Research limitations/implicationsThe authors used a cross-sectional design to collect responses and ensured the absence of common method variance through Harman's Single factor test.Originality/valueThis study identified the mechanism (job satisfaction and POS) through which benevolent, moral and authoritative dimensions of PL predict turnover intention among nurses working in high power distance culture.

Health assumptions to the population due to the utilization of contaminated vegetables have been a great concern all over the world. In this study, an investigation has been conducted to ascertain metal concentrations in the wastewater, soil and commonly consumed vegetables from the vicinity of Gadoon Industrial Estate Swabi, Khyber Pakhtunkhwa Pakistan. Physicochemical parameters such as pH, electrical conductivity (EC), total dissolved solids (TDS), total suspended solids (TSS) and total solids (TS) and heavy metals such as Pb, Cr, Cd, Ni, Zn, Cu, Fe, Mn were determined using Atomic Absorption Spectrophotometer (AAS). Moreover, possible health risks due to the consumption of vegetables have also been estimated. pH and TSS in wastewater were found to be higher than the permissible limit set by WHO (1996). These results revealed that Cr concentration in the wastewater was above the permissible limits of United States Environmental Protection Agency (USEPA) which may lead to a detrimental effect on soil quality deterioration, ultimately leading to food contamination. ANOVA analysis demonstrated a significant difference in soil samples for Pb, Cr, Cd, Ni, Zn and Cu at p ≤ 0.001, for Mn at p ≤ 0.05 while no significant difference was observed for Fe respectively. ANOVA analysis also exhibited the highest mean value for Pb, Cr, Cd and Zn in vegetables. A substantial positive correlation was found among the soil and vegetable contamination. The transfer factor for Cr, Pb, Zn, Mn, Ni, Cd and Cu was greater than 0.5 due to contamination caused by domestic discharges and industrial effluents. Health assessment via consumption of dietary vegetables revealed a higher level than the permissible limit (HRI > 1) for Pb and Cd in children and adults. Enrichment factor (EF) due to consumption of vegetables was found higher for Pb and Cr respectively. Based on the findings of this study, there would be a significant risk to the consumers associated with consumptions of vegetables being cultivated in Gadoon Industrial Estate area of district Swabi. Therefore, strict regulatory control measures are highly recommended for the safety of vegetables originated from the study area.

Humanpapillomavirus (HPV) has infected nearly 80 million people in the U.S., and is associated with most cervical cancer cases. Alabama ranks first in the country for cervical cancer mortality and third for incidence. Although the HPV vaccine can prevent HPV and reduce cancer rates, Alabama is well-below the national average for HPV vaccination. Using the Theory of Planned Behavior (TPB), this Alabama-based study aimed to examine college students’ intentions to get the HPV vaccine; to examine the relationship between the relationship between religious beliefs and HPV vaccination uptake status among college students. Students (n = 257) from a university in rural Alabama completed the survey. Multiple regression analysis, Mann-Whitney U tests, and moderation analysis were used to examine associations among the variables of interest. Consistent with TPB, results showed that attitudes and subjective norms were significant predictors of intention to get vaccinated. Knowledge that both sexes can experience HPV-related health problems, that HPV can cause genital warts, and that the vaccine protects against HPV were each associated with higher attitude scores. The results indicated that the odds of getting at least one HPV shot were higher for females than for males for non-Caucasians than for Caucasians. Students who were not vaccinated were more likely to report that religion influenced their health beliefs. *Abstract. TPB was helpful in understanding HPV-related intentions. Communication and education efforts are needed to increase understanding of HPV illnesses and HPV vaccination benefits among peers, parents, and other loved ones of students. in the rural areas of Alabama.

The purpose of this study was to determine the anticancer potential of Ifloga spicata ( I. spicata ) against HepG-2 cell line. To assess I. spicata cytoxicity, brine shrimp lethality and MTT assays were performed. In the brine shrimp bioassay, the ethyl acetate fraction had a significant impact with an IC 50 of 10 μg/ml. The ethyl acetate and chloroform fractions inhibited HepG-2 cell line effectively (IC 50 values 5.54 and 6.52 μg/ml, respectively). The isolated compound, heptadecyl benzoate inhibited growth significantly (IC 50 , 8.92 μg/ml) while methyl dihydroxybenzoate had modest activity (25.66 μg/ml) against the cell line. Both compounds displayed acceptable pharmacokinetic parameters in the ADME study. In the docking study, the methyl dihydroxybenzoate was involved in two hydrogen bonds with two different residues Thr830 and Asp831. The heptadecyl benzoate carbonyl oxygen exhibited a single hydrogen bond with Lys692. Both showed good interactions with the active site of the (EGFR) tyrosine kinase. Our findings suggest that I. spicata might be a viable source of anticancer natural agents. This discovery raises the prospect of the future development of a new medication for the treatment of liver cancer.

Ginkgo biloba extract possess several promising biological activities; currently, it is clinically employed in the management of several diseases. This research work aimed to extrapolate the antioxidant and anti-inflammatory effects of Ginkgo biloba (Gb) in methotrexate (MTX)-induced liver toxicity model. These effects were analyzed using different in vivo experimental approaches and by bioinformatics analysis. Male SD rats were grouped as follows: saline; MTX; Gb (pretreated for seven days with 60, 120, and 180 mg/kg daily dose before MTX treatment); silymarin (followed by MTX treatment); Gb 180 mg/kg daily only; and silymarin only. Histopathological results revealed that MTX induced marked hepatic injury, associated with a substantial surge in various hepatic enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and serum alkaline phosphatase (ALP). Furthermore, MTX caused the triggering of oxidative distress associated with a depressed antioxidant system. All these injury markers contributed to a significant release of apoptotic (caspase-3 and c-Jun N-terminal kinases (JNK)) and tumor necrosis factor (TNF-α)-like inflammatory mediators. Treatment with Gb counteracts MTX-mediated apoptosis and inflammation dose-dependently along with modulating the innate antioxidative mechanisms such as glutathione (GSH) and glutathione S-transferase (GST). These results were further supplemented by in silico study to analyze drug-receptor interactions (for several Gb constituents and target proteins) stabilized by a low energy value and with a good number of hydrogen bonds. These findings demonstrated that Gb could ameliorate MTX-induced elevated liver reactive oxygen species (ROS) and inflammation, possibly by JNK and TNF-α modulation.