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The present study was aimed to assess the nephroprotective effect of Cressa cretica hydroalcoholic extract (CCE) on VAN-triggered renal toxicity in rabbits. Total phenolic and flavonoid contents found in CCE were 30.92 ± 2.93 mg GAE/g extract and 11.87 ± 1.70 mg CE/g extract, respectively. The CCE demonstrated a significant 2,2-diphenyl-1-picrylhydrazyl radical (DPPH*) scavenging ability with an IC50 value of 24.99 µg/mL. To evaluate the nephroprotective potential of CCE, thirty-six rabbits were divided into six groups (n = 6) and treated for consecutive 14 days as G-I: normal control, G-II: vehicle control (VAN 200 mg/kg, i.p.), G-III: SIL (silymarin 150 mg/kg, i.g. + VAN-treated), and G-IV to VI: CCE at 200, 400, and 600 mg/kg, i.g. + VAN-treaded groups. Blood samples were withdrawn at the 0th, 7th, and 14th days of the experiment for biochemical analysis, and renal tissues were collected at the end of experiment for antioxidant/oxidant markers and histopathological assessments. VAN significantly (P

This study was aimed to phytochemically characterize and assess the antioxidant activities of 70% methanol extract and subsequent fractions of Cassia absus (L.) seeds, Gymnema sylvestre (L.) whole plant, Nigella sativa (L.) seeds, and Piper nigrum (L.) seeds. Powdered plant materials were extracted with 70% methanol and further fractionated with ethyl-acetate, n-butanol and the residual aqueous fraction. Phytochemical analysis was performed to detect different phytocompounds. Mineral compositions were quantified, and total phenolic and flavonoid contents were determined. The antioxidant potential of methanol extracts and fractions was assessed in vitro through estimating DPPH radical and superoxide anion scavenging activities and reducing power assay. Extraction yields ranging highest of N. sativa methanol extract (30.42�1.49%) and lowest of P. nigrum ethyl-acetate fraction (4.58�0.61%) were obtained. Results revealed that methanol extracts and fractions of selected plants contain phytocompounds such as alkaloids, flavonoids, phenols, glycosides, tannins, terpenoids, saponins, carbohydrates, fats and fixed oils. The mineral analysis showed considerable quantities of calcium (C. absus methanol extract: 372.454�3.633 mg/100g), magnesium (G. sylvestre methanol extract: 131.045�1.346 mg/100g), and zinc (N. sativa methanol extract: 36.019�0.284 mg/100 g) in all fractions while minor quantities of manganese, copper and cobalt were also found. Methanol extracts showed considerably higher total phenolic (N. sativa methanol extract: 179.71�2.14 mg GAE/g) and flavonoid (N. sativa methanol extract: 189.18�3.17 mg CE/g) contents compared to other fractions, and subsequently exhibited pronounced scavenging activities on DPPH* (N. sativa methanol extract: 23.8 �g/mL) and superoxide radicals (N. sativa methanol extract: 24.9 �g/mL) and had potent reductive abilities (N. sativa methanol extract: 1.123�0.038 O.D.). Conclusively, C. absus, G. sylvestre, N. sativa and P. nigrum possess significant nutritive properties and could be used as natural antioxidant sources to prevent oxidative stress-associated diseases.

A cross sectional study was performed to determine the frequency of Escherichia coli in fresh and frozen meat samples followed by antimicrobial resistance profiling and to detect different extended spectrum beta lactamases (ESBLs) genes. A total of 100 samples of fresh and frozen meat (n=50 each) were collected from different butcher shops and supermarkets. Equal numbers of specimens were collected from chicken and mutton. Samples were processed for isolation and identification of E. coli by standard microbiological, biochemical and molecular characterization. The resistance pattern was detected by Kirby-Bauer disk diffusion method while presence of ESBLs was checked by double disk synergy test and PCR. The results of present study showed that among 100 meat samples, potentially pathogenic E. coli was isolated from 36 samples with greater contamination 20/50 (40%) in chicken samples in comparison to mutton 16/50 (32%). Similarly, the frequency of E. coli was more pronounced in fresh meat 30/50 (60%) rather than frozen 4/50 (8%). The highest resistance pattern (100%) was observed against ampicillin, ciprofloxacin, vancomycin and tetracycline followed by cefotaxime (91.6%) and (n=27) isolates were found multi drug resistant (MDR). The double disk synergy test found 17 (47.22%) ESBL producing isolates while bla CTX-M gene was identified in 5 (29.41%) isolates followed by bla OXA-48 in 4 (23.52%) samples and bla TEM gene in 1 (5.88%). This study revealed that vigilant control procedures should be implemented all over the food chain and effective surveillance should also be performed at national level to minimize the spread of MDR and ESBL producing Escherichia coli from raw meat.

Sana Ilyas,1 Muhammad Hidayat Rasool,1 Muhammad Javed Arshed,2 Muhammad Usman Qamar,1 Bilal Aslam,1 Ahmad Almatroudi,3 Mohsin Khurshid1 1Department of Microbiology, Government College University, Faisalabad, Pakistan; 2National Veterinary Laboratory, National Agriculture Research Council, Islamabad, Pakistan; 3Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi ArabiaCorrespondence: Muhammad Hidayat RasoolDepartment of Microbiology, Government College University, Faisalabad 38000, PakistanTel +92 41-9203023Email drmhrasool@gcuf.edu.pkBackground and Aim: The extended-spectrum beta-lactamases (ESBLs), as well as carbapenemases, are considered as the foremost resistance determinants throughout the world. However, the relevant data especially related to the sequence types of ESBL and carbapenemases producing Escherichia coli from the poultry is limited from Pakistan. Here, we present the data on the genetic diversity of E. coli strains isolated from the poultry birds from the poultry farms located in Islamabad, Pakistan, and the underlying resistance mechanisms to beta-lactam agents.Methods: Of 250 broilers from 25 different farms (10 birds from each farm), the cecal samples were obtained and analyzed for the presence of ESBLs producing E. coli (ESBL-Ec) as well as carbapenemases producing E. coli (CPEc) strains using selective agar for ESBL and carbapenemases screening. The susceptibility profiling of the ESBL-Ec and CPEc isolates was evaluated followed by multi-locus sequence typing.Results: A total of 119 strains were positive for ESBL production whereas 37 strains were found positive to produce carbapenemases in addition to ESBLs. The MLST analysis has shown a diversity of isolates as the E. coli isolates from poultry birds correspond to a total of 16 sequence types (STs). The ST131 (22/48, 46%) followed by ST8051 (10/48, 21%) were the main STs in this study. The blaCTX-M gene was detected in all the poultry E. coli strains whereas the blaTEM was found in 45.5% of strains. The blaVIM was found in all 37 CPEc isolates whereas the blaNDM and blaIMP were found in 31/37 (83.8%) and 16/37 (43.2%) CPEc isolates respectively.Conclusion: The overall results have shown the prevalence of diverse genotypes among the ESBL-Ec and carbapenemase-producing E. coli (CPEC) from poultry. Furthermore, the study documents poultry birds as a persisting reservoir of extensively antimicrobial-resistant E. coli ST131 in Pakistan, suggesting a potential threat to public health.Keywords: MLST, E. coli, poultry, Pakistan, AMR, ESBL

Nigella sativa and Piper nigrum are implicated in the treatment of various disorders, especially in the management of metabolic, infectious and hepatorenal ailments. However, data on the mechanism behind therapeutic potential of N. sativa and P. nigrum in liver diseases is scarce. The present study investigated the hepatoprotective potential of 70% methanolic extract of N. sativa (NSE) and P. nigrum (PNE) at varying dose levels (100 to 400 mg/kg body weight) against concanavalin A (conA)-induced liver injury. Qualitative phytochemical analysis of plant extracts was performed. Acute hepatic injury was induced by administering intraperitoneally 12mg/kg conA in Balb/c mice. The extent of hepatic injury was measured by analysing serum biochemical parameters, liver antioxidant stress assay and histopathology. Data were analysed statistically. NSE and PNE showed dosedependent hepatoprotective efficacy by lowering the conA-dependent rise in liver transaminase level. Treatment with NSE (400 mg/Kg) and PNE (400 mg/Kg) ameliorated conA-induced alterations in serum oxidative stress markers, biochemical parameters, liver function markers and histopathology. NSE indicated greater effectiveness to ameliorate the acute hepatic injury in comparison with PNE at the same dose. Collectively, pretreatment with NSE and PNE attenuated the liver injury induced by conA, might be through alleviating the antioxidant capacity of experimental mice

Organophosphates are highly toxic compounds as they are involved in irreversible inhibition of acetylcholinesterase, causing various neurotoxic effects via acetylcholine accumulation throughout the nervous system. Traditional treatments for organophosphate poisoning are not effective enough to overcome all the toxic effects. There is a need for alternate treatment of life threatening poisoning of organophosphates. For this purpose a biomimetic nanosponge of poly (lactic- co-glycolic acid) is prepared, characterized and analysed as an antidote for organophosphate poisoning. In this nanosponge red blood cell membranes are used for coating poly lactic co-glycolic acid nanoparticles. In vitro studies are conducted to investigate the retention of acetylcholinesterase activity on the prepared nanosponge as well as to assess the scavenging ability of prepared nanosponge for model organophosphate, chlorpyrifos. In vivo studies are conducted to evaluate the detoxification potential of nanosponge in rabbit model, poisoned with chlorpyrifos. Hepatotoxicity and renal toxicity of nanosponge/chlorpyrifos complex is also studied in survived rabbits and the data is analysed statistically.

Ocimum sanctum L. is widely used as traditional remedy to manage hyperglycemia. This study was aimed to evaluate the effect of aqueous-methanolic extract of O. sanctum leaves (OSE) on the anti-diabetic activity of gliclazide in alloxan-induced diabetes in Wistar rats. Diabetes was induced by intraperitoneally injecting alloxan (120 mg/kg b.w.) in rats. Treatments including OSE (100 mg/kg b.w.), gliclazide (100 mg/kg b.w.), and in combination were given daily to diabetic rats till the 21st day of study. Body weight and fasting blood glucose levels were determined at regular intervals, while blood and organ samples were taken at the end of the study for biochemical and histopathological studies. Results showed that treatments exhibited anti-hyperglycemic activity through significantly (p [ 0.05) restoring body weight, fasting blood glucose level, and serum levels of glucose, insulin and HbA1c. The anti-lipidemic activity was noticed as total cholesterol (TC), triglyceride (TG), high-/low density-lipoproteins (HDL-C, LDL-C) levels were restored in treated diabetic rats. Ameliorative effects of treatments were observed as significant (p [ 0.05) reduction in serum levels of liver function biomarkers (alanine aminotransferase; ALT, aspartate aminotransferase; AST, alkaline phosphatase; ALP and bilirubin; BIL) and restoration of oxidative stress biomarkers (catalase; CAT, superoxide dismutase; SOD and malondialdehyde; MDA) in liver tissue. Histopathological findings supported these results as an increase in pancreatic islets size and protective effects on liver tissue was observed in diabetic rats treated with gliclazide and OSE alone and their combination. Conclusively, the combination of OSE and gliclazide produced a synergistic anti-diabetic effect as compared to that of alone treatment.

High fat high sugar (HFHS) diet results in various disorders including oxidative stress. In present study, prebiotics supplementation was given to rats following HFHS diet feeding. The results showed that prebiotics significantly lowered the HFHS-diet associated elevated levels of cholesterol, triglyceride, low density lipids, alkaline phosphatase, blood urea, creatinine, uric acid and total proteins. Prebiotics significantly restored the HFHS-diet induced decrease in total anti-oxidant capacity. The levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, total oxidation status, malondialdehyde, paraoxonase and arylesterase were not significantly different in HFHS-Prebiotics group as compared to control group. Histological analyses of liver, intestine and kidney tissues in HFHS-group showed cytoplasmic vacuolation, mucosal damage, hepatic triad abnormalities, eccentric nuclei, focal necrosis, tubular congestion and neutrophil infiltration which were significantly improved in HFHS+Prebiotics group suggesting ameliorative potential of prebiotics. In conclusion, our results demonstrated that prebiotics possess therapeutic potential in ameliorating HFHS-diet associated alterations in metabolic profile, oxidative stress markers and histological architecture in intestine, liver and kidney tissues

The evolution of antimicrobial-resistant Gram-negative pathogens is a substantial menace to public health sectors, notably in developing countries because of the scarcity of healthcare facilities. New Delhi metallo-β-lactamase (NDM) is a potent β-lactam enzyme able to hydrolyze several available antibiotics. NDM was identified from the clinical isolates of Klebsiella pneumoniae and Escherichia coli from a Swedish patient in New Delhi, India. This enzyme horizontally passed on to various Gram-negative bacteria developing resistance against a variety of antibiotics which cause treatment crucial. These bacteria increase fatality rates and play an integral role in the economic burden. The efficient management of NDM-producing isolates requires the coordination between each healthcare setting in a region. In this review, we present the prevalence of NDM in children, fatality and the economic burden of resistant bacteria, the clonal spread of NDM harboring bacteria and modern techniques for the detection of NDM producing pathogens.

Introduction Intense livestock farming practices enforcing the farmers to use antibiotics as food supplements on a routine basis. Aberrant use of antibiotics is associated with the emergence of antibiotics resistance and resistant superbugs. Keeping in view the current scenario, the present study was designed for the first time from Pakistan with a specific aim to estimate the prevalence of the carbapenem-resistant Klebsiella pneumoniae in veterinary settings and the waste in Pakistan. Methods A total of 138 samples from various veterinary sources were collected by employing a nonprobability sampling technique. Isolation and phenotypic identification of carbapenem-resistant K. pneumoniae were performed according to the CLSI standard. Molecular detection of various antibiotic resistance genes (ARGs) was done through PCR by using specific primers against each ARG. According to the pasture scheme, the multilocus sequence typing (MLST) was performed to characterize the K. pneumoniae sequence types (STs). Results According to the results of the study, overall 9.4% (13/138) isolates were confirmed carbapenem-resistant K. pneumoniae. Among various carbapenem ARGs particularly, the bla NDM-1 was found in 92.3% (12/13) isolates followed by bla OXA-48 84.6% (11/13). MLST results revealed that overall 3 STs were found in the study which includes ST29, ST11, and ST258. Taking together, this is the first study to our best knowledge which demonstrated the prevalence of carbapenem-resistant K. pneumoniae and its various STs prevalent in veterinary settings and the waste of Pakistan. Conclusion Based on the above-mentioned facts, we suggested that veterinary settings and waste are the potential source and reservoir of carbapenem-resistant K. pneumoniae, which may be disseminated to the environment and ultimately can affect the public and companion livestock health.

Introduction The aminoglycosides are widely used for the therapeutic management of infections caused by gram-negative bacteria, including the Acinetobacter baumannii strains. However, the resistance to the members of the aminoglycoside family, such as amikacin, gentamicin, and tobramycin, is increasingly being common among the clinical isolates. Purpose This study aimed to investigate the presence of 16SrRNA methylases and aminoglycoside modifying enzymes (AMEs) genes among aminoglycoside resistant A. baumannii isolates and to study the genetic diversity of the clinical population of A. baumannii in local hospitals. Material and methods The 143 A. baumannii clinical strains were analyzed for antimicrobial susceptibility, genetic screening for enzymes conferring aminoglycosides resistance followed by the multilocus sequence typing. Results The 133/143 (93%) isolates were non-susceptible to at least one of the tested aminoglycosides, including amikacin, gentamicin, and tobramycin. The MIC distribution has shown that 87.486.7% strains were resistant to amikacin and gentamicin, respectively. The aphA6, aadB, aacC1, and aphA1 were found in 74.1%, 59.4%, 16.1%, and 11.2% isolates, respectively, whereas the armA was found in 28% of the strains having a higher MIC value (MIC; ≥256µg/mL). The MLST data have shown that the ST589 and ST2 were the most common STs and corresponded to 51 (35.7%) and 38 (26.6%) isolates, respectively, and few of the isolates corresponding to these STs were found to harbor the armA gene with a variable genotypic profile for AMEs. Discussion The study has reported the incidence of various enzymes conferring aminoglycoside resistance among the A. baumannii clones for the first time from Pakistan. The findings suggest the possibility of transmission of aminoglycoside resistance determinants through the lateral gene transfer as well as clonal dissemination.

Klebsiella pneumoniae is an important pathogen that causes pneumonia and bloodstream infections, especially in neonates and intensive care patients. The carbapenems remain an important therapeutic option for clinicians, particularly against cephalosporin-resistant Gram-negative pathogens. This increased use of carbapenems at clinics has resulted in the evolution and spread of carbapenem-resistant K. pneumoniae. In this study, we isolated six bla K. pneumoniae carbapenemase (KPC)-producing strains belonging to sequence type 258 (ST258) from clinical, environmental, and veterinary sources. Antibiotic susceptibility was performed on these isolates and the genes responsible for extended-spectrum beta-lactamases and metallo-beta-lactamase production were screened. The molecular typing was done using multilocus sequence typing. Isolated strains were resistant to various antibiotic classes, including carbapenems, and carried the carbapenem-resistant gene, blaKPC. All strains were susceptible to tigecycline and colistin. This is the first report detecting K. pneumoniae ST258 strains in Pakistan.

Antibiotic resistance against present antibiotics is rising at an alarming rate with need for discovery of advanced methods to treat infections caused by resistant pathogens. Silver nanoparticles are known to exhibit satisfactory antibacterial and antibiofilm activity against different pathogens. In the present study, the AgNPs were synthesized chemically and characterized by UV-Visible spectroscopy, scanning electron microscopy, and X-ray diffraction. Antibacterial activity against MDR K. pneumoniae strains was evaluated by agar diffusion and broth microdilution assay. Cellular protein leakage was determined by the Bradford assay. The effect of AgNPs on production on extracellular polymeric substances was evaluated. Biofilm formation was assessed by tube method qualitatively and quantitatively by the microtiter plate assay. The cytotoxic potential of AgNPs on HeLa cell lines was also determined. AgNPs exhibited an MIC of 62.5 and 125 μg/ml, while their MBC is 250 and 500 μg/ml. The production of extracellular polymeric substance decreased after AgNP treatment while cellular protein leakage increased due to higher rates of cellular membrane disruption by AgNPs. The percentage biofilm inhibition was evaluated to be 64% for K. pneumoniae strain MF953600 and 86% for MF953599 at AgNP concentration of 100 μg/ml. AgNPs were evaluated to be minimally cytotoxic and safe at concentrations of 15-120 μg/ml. The data evaluated by this study provided evidence of AgNPs being safe antibacterial and antibiofilm compounds against MDR K. pneumoniae.

Objective To assess the association between triglycerides (TG), total cholesterol (TC) and hyperuricemia (HUA) in the general Chinese population. Methods A population-based cross-sectional survey included 9680 participants aged 35-74 years in 2006 and 2009 in Qingdao, China. TG, TC and uric acid (UA) were measured. The logistic regression model was performed to estimate the association between TG, TC, and HUA with an odds ratio (OR) and 95% confidence intervals (CI). Meanwhile, age stratification analysis (

The New Delhi Metallo-β-lactamase (NDM) producing Enterobacteriaceae is spreading worldwide. Although the blaNDM gene has been identified in animal associated Enterobacteriaceae isolates in many countries, little is known about its occurrence in animal products in Pakistan. In this study, 13 Escherichia coli isolates were collected from chicken meat samples in Pakistan. Two isolates, 15978 and C4109, exhibited reduced susceptibility (MIC ≥1 μg/mL) to imipenem, and carried blaNDM-5 and blaNDM-7 gene, respectively. Whole-genome sequencing and Oxford Nanopore MinION sequencing revealed that 15978 and C4109 belonged to ST156 and ST167, respectively. blaNDM-7 was carried by an IncX3 plasmid that has disseminated worldwide, whereas blaNDM-5 was located on an F36: A-: B32 plasmid, which shared high identity with two plasmids carried by E. coli isolates from other countries (one from a patient in Canada). To the best of our knowledge, this is the first report characterizing blaNDM-carrying plasmids from chicken meat samples in Pakistan. The dissemination of almost identical blaNDM-5-bearing F36:A-:B32 and blaNDM-7-bearing IncX3 plasmids in different countries highlights the importance of international trade and travel in the spread of antimicrobial resistance strains and plasmids worldwide.

Antibiotic resistance (ABR) is a growing public health concern worldwide, and it is now regarded as a critical One Health issue. One Health’s interconnected domains contribute to the emergence, evolution, and spread of antibiotic-resistant microorganisms on a local and global scale, which is a significant risk factor for global health. The persistence and spread of resistant microbial species, and the association of determinants at the human-animal-environment interface can alter microbial genomes, resulting in resistant superbugs in various niches. ABR is motivated by a well-established link between three domains: human, animal, and environmental health. As a result, addressing ABR through the One Health approach makes sense. Several countries have implemented national action plans based on the One Health approach to combat antibiotic-resistant microbes, following the Tripartite’s Commitment Food and Agriculture Organization (FAO)-World Organization for Animal Health (OIE)-World Health Organization (WHO) guidelines. The ABR has been identified as a global health concern, and efforts are being made to mitigate this global health threat. To summarize, global interdisciplinary and unified approaches based on One Health principles are required to limit the ABR dissemination cycle, raise awareness and education about antibiotic use, and promote policy, advocacy, and antimicrobial stewardship.

Antibiotic exposure leads to massive selective pressures that initiate the emergence and spread of antibiotic resistance in commensal and pathogenic bacteria. The slow process of developing new antibiotics makes this approach counterintuitive for combatting the rapid emergence of new antibiotic resistant pathogens. Therefore, alternative approaches such as, the development of nucleic acid-based anti-bacterial treatments, anti-bacterial peptides, bacteriocins, anti-virulence compounds and bacteriophage therapies should be exploited to cope infections caused by resistant superbugs. In this editorial, we discuss how the newly popular CRISPR-Cas system has been applied to combat antibiotic resistance.

Herbal therapies always remain a potential source of glycemic control in diabetic patients. Plants or combination of plants improve the healing action and lessen the adverse effects compared to synthetic drugs. The present research was designed to evaluate antidiabetic potential of polyherbal formulation consisting of Sphaeranthus indicus, Caesalpinia bonduc, Bunium persicum, Artemisia absinthium, Cuminum cyminum, Swertia chirata, Gymnema sylvestra, and Citrullus colocynthis in alloxanized diabetic rats. Quantitative phytochemical, RP-HPLC, DPPH and in vitro alpha amylase analyses of formulation were performed. Rats were grouped into six groups (n=15/group) named as control, diabetic control, glibenclamide treated, Treated I, Treated II and Treated III. Hyperglycemic rats of treated groups I, II and III were administered polyherbal formulation at dose rate of 200, 400 and 600mg/kg respectively for 8 weeks after induction of diabetes with alloxan monohydrate (150, IP). The results have shown that alloxan significantly increased fasting blood glucose (531.81±4.29) and serum glucose (526.0±6.26) levels. However, 8-weeks treatment of hyperglycemic rats with polyherbal formulation significantly decreased the fasting blood glucose (156.82±4.51), serum glucose (148.8±4.04) and increased C-peptide and liver glycogen levels. The levels of ALT, AST, ALP, TAC and TOS were also restored towards normal. Histopathological analysis of pancreas also showed increase in size and number of pancreatic β cells after polyherbal formulation treatment compared to diabetic group. This study shows that polyherbal formulation has antidiabetic potential as it can improve performance of pancreatic β cells and insulin secretory capacity by reducing hyperglycemia and oxidative stress induced β cells apoptosis

The Qingdao diabetes risk score (QDRS) is an accurate tool for identifying individuals who are at a high risk for diabetes. This study was designed to determine the association of the QDRS with the incidence of diabetes in the general population in urban and rural settings. A stratified, random, cluster-sampling method was used to select representative individuals in 2006 and 2009, and the follow-up survey was conducted from 2012 to 2015. Of 5851 participants, 3248 were available in cohort study. The individuals without data of FPG, 2 h PG was excluded in follow-up survey. Finally, a total of 3033 participants were included. Waist circumference, age, and family history of diabetes were collected to determine the QDRS. Cox proportional hazards regression models were used to evaluate the association of QDRS and BMI with the incidence of diabetes. Further, we assessed the relative excess risk due to interaction (RERI), synergy index (S), and attributable proportion due to interaction (AP). Their age-standardized cumulative incidence of diabetes was 16.9% and 10.8% among the urban and rural populations, respectively. In both urban and rural settings, individuals with a QDRS ≥ 14 had a significantly higher risk for diabetes than the individuals with a QDRS

Objective Current study was designed to isolate the pathogens from burn wounds and determine the antibiogram of these isolates. Methods A total of 85 samples were collected from burn patients with the history of different weeks of hospitalization in various public and private hospitals of Faisalabad during September 2017-July 2019 and shifted to Department of Microbiology, Government College University, Faisalabad for further processing. Isolation and identification of the pathogens was done through conventional microbiological procedures. Disc diffusion method was used for the determination of antibacterial and antifungal activity. Results A total of 40(91%) samples were found positive for the presence of bacterial or fungal pathogens. Commonly isolated pathogens were Staphylococcus aureus 15 (21.4%), Pseudomonas aeruginosa 15 (21.4%), Bacillus subtilis 11(15.7%), Escherichia coli 10(14.2%), Candida albicans 8(11.4%), Aspergillus flavus 6(8.5%) and Salmonella Typhi 5(7.1%). Highest resistance was found against S. aureus and P. aeruginosa. Cefotaxime was the least effective antibiotic, while Gentamicin and Amphotericin-B were the mosteffective antimicrobial drugs against bacterial and fungal pathogens, respectively. Conclusions Taking together it was concluded that most isolated pathogen was S. aureus and P. aeruginosa followed by B. subtilis, E. coli, C. albicans, A. flavus and S. typhi from burn wound in hospitalized patients. Anti-biogram studies showed S. aureus and P. aeruginosa were the most resistant pathogens whereas S. typhi, C. albicans and A. flavus were susceptible to various commonly used antibiotics. Cefotaxime was the least effective antibiotic, while Gentamicin and Amphotericin-B were the most effective antimicrobial drugs against bacterial and fungal pathogens, respectively. It is suggested that alternate anti-microbial agents should be investigated to control the infections.

Background: Depression is a common mental illness. Previous studies suggested that health conditions and lifestyle factors were associated with depression. However, only few studies have explored the risk factors of depression in a large representative sample of the general population in the world.Methods: A population-based cross-sectional survey was conducted in the 2006 survey and 2009 survey in Qingdao, China. The participants with insufficient information were excluded: Zung score, body mass index (BMI), diabetes items, physical activity, smoking, or drinking. Finally, a total of 3,300 participants were included in this analysis. The category of depression was used in the Zung self-rating depression scale (ZSDS). The associations between different indicators of health conditions (diabetic status, BMI), lifestyle factors (physical activity, smoking, and alcohol consumption), and depression were assessed by the logistic regression model.Results: The mean Zung scores for all participants, male participants, and female participants were 29.73 ± 7.57, 28.89 ± 7.30, 30.30 ± 7.70, respectively. In all participants, those who were pre-diabetes status (OR: 1.53, 95% CI: 1.04–2.27), and irregular physical activity (OR: 0.39, 95% CI: 0.17–0.89) had an increased risk of depression. In man, the analysis showed an increased risk of depression those with pre-diabetes (OR: 2.49, 95% CI: 1.25–4.97), previously diagnosed diabetes (OR: 4.44, 95% CI: 1.58, 12.48), and in those irregular activities (OR: 0.07, 95% CI: 0.01–0.61). In women, those who were underweight (OR: 5.66, 95% CI: 1.04–30.71) had a greater risk of depression.Conclusions: These results suggested that health conditions and lifestyle factors were the potential risk factors for depression. Men with pre-diabetes, previously diagnosed diabetes, and irregular activity had an increased risk for depression; women with underweight status had a higher risk for depression.

Emergence of multidrug resistant pathogens is increasing globally at an alarming rate with a need to discover novel and effective methods to cope infections due to these pathogens. Green nanoparticles have gained attention to be used as efficient therapeutic agents because of their safety and reliability. In the present study, we prepared zinc oxide nanoparticles (ZnO NPs) from aqueous leaf extract of Acacia arabica. The nanoparticles produced were characterized through UV-Visible spectroscopy, scanning electron microscopy, and X-ray diffraction. In vitro antibacterial susceptibility testing against foodborne pathogens was done by agar well diffusion, growth kinetics and broth microdilution assays. Effect of ZnO NPs on biofilm formation (both qualitatively and quantitatively) and exopolysaccharide (EPS) production was also determined. Antioxidant potential of green synthesized nanoparticles was detected by DPPH radical scavenging assay. The cytotoxicity studies of nanoparticles were also performed against HeLa cell lines. The results revealed that diameter of zones of inhibition against foodborne pathogens was found to be 16–30 nm, whereas the values of MIC and MBC ranged between 31.25–62.5 μg/ml. Growth kinetics revealed nanoparticles bactericidal potential after 3 hours incubation at 2 × MIC for E. coli while for S. aureus and S. enterica reached after 2 hours of incubation at 2 × MIC, 4 × MIC, and 8 × MIC. 32.5–71.0% inhibition was observed for biofilm formation. Almost 50.6–65.1% (wet weight) and 44.6–57.8% (dry weight) of EPS production was decreased after treatment with sub-inhibitory concentrations of nanoparticles. Radical scavenging potential of nanoparticles increased in a dose dependent manner and value ranged from 19.25 to 73.15%. Whereas cytotoxicity studies revealed non-toxic nature of nanoparticles at the concentrations tested. The present study suggests that green synthesized ZnO NPs can substitute chemical drugs against antibiotic resistant foodborne pathogens.

Introduction The mounting incidence of multidrug-resistant bacterial strains and the dearth of novel antibiotics demand alternate therapies to manage the infections caused by resistant superbugs. Bacteriophages and phage=derived proteins are considered as potential alternates to treat such infections, and have several applications in health care systems. The aim of this review is to explore the hidden potential of bacteriophage proteins which may be a practical alternative approach to manage the threat of antibiotic resistance. Results Clinical trials are in progress for the use of phage therapy as a tool for routine medical use; however, the existing regulations may hamper their development of routine antimicrobial agents. The advancement of molecular techniques and the advent of sequencing have opened new potentials for the design of engineered bacteriophages as well as recombinant bacteriophage proteins. The phage enzymes and proteins encoded by the lysis cassette genes, especially endolysins, holins, and spanins, have shown plausible potentials as therapeutic candidates. Conclusion This review offers an integrated viewpoint that aims to decipher the insights and abilities of bacteriophages and their derived proteins as potential alternatives to antibiotics.

Background: K. pneumoniae is ubiquitous and known to be a notorious pathogen of human, animal, and plant-based food. K. pneumoniae is a recognized trafficker of antibiotic resistance genes (ARGs) between and from different ecological niches. Current study was designed to decipher the transmission dynamics and genetic relatedness of MDR K. pneumoniae at the human-animal-environment interface in Pakistan. Methods: A total (n=775) samples were collected from September 2017 to August 2019 from the human, animal, and environmental sources by applying the convenient random sampling technique. HiChrome Klebsiella Selective agar (Himedia®) was used for the isolation of K. pneumoniae, VITEK™ identification system (bioMerieux, France) was used isolates identification. CLSI guidelines 2018 were followed for antibiotic susceptibility testing. The range of antibiotic resistance genes (ARGs) was detected through PCR by using specific primers. Multi Locus Sequence Typing (MLST) was performed according to the Pasteur scheme and sequence types (STs) were allotted to the isolates. Findings: A total of 120 (15.7 %) samples were confirmed K. pneumoniae. The distribution of K. pneumoniae among humans, animals, and the environment were 17.4 %, 15.17%, and 7.9 % respectively. Isolates have shown significant resistance against all the subjected antibiotics except colistin. In acquired resistance genes, the highest percentage prevalence (67.5 %) of blaCTX-M was estimated in the isolates, various carbapenem resistance genes that were found in the study were blaNDM-1 (43.3%), blaOXA-48 (38 %), and (1.67 %) blaKPC-2. Conclusion: Overall, 21 distinct sequence types (STs) and 13 clonal complexes (CCs) were found through the MLST analysis. Taking together, the dissemination of genetically related K. pneumoniae clones among the community is alarming for the health care system of the country. Health policymakers should consider the role of all the integral parts of human, animal, and associated environment intently to cope with this serious public and animal health concern. Funding Statement: This study was supported by grants from the major science and technology special project of Yunnan Province, No. 2019ZF004. Declaration of Interests: All author declare No conflict of interests. Ethics Approval Statement: The study was conducted in a span of two years duration from September 2017 to August 2019; proper permission was granted by the Ethical Review Board (ERB) of Government College University, Faisalabad, Pakistan.

Background. The term “persisters” refers to a small bacterial population that persists during treatment with high antibiotic concentration or dose in the absence of genetic resistance. The present study was designed to investigate the transcriptional response in indigenous Klebsiella pneumoniae under the ciprofloxacin stress. Methods. Isolation and identification of K. pneumoniae were carried out through standard microbiological protocols. The characterization of quinolone resistance was performed by estimating the quinolone susceptibility testing, MIC estimation, and detecting the QRDR and PMQR. Transcriptional response of the isolates to ciprofloxacin was determined using qPCR. Results. Among 34 isolates, 23 (67%) were resistant to ciprofloxacin. Both QRDR (gyrA and gyrB) and PMQR (qnrA, qnrB, and qnrS) were detected in the isolates, and all were found resistant to ciprofloxacin. The mRNA levels of both mutS and euTu under the influence of ciprofloxacin were significantly increased. On ciprofloxacin exposure, the mRNA levels of the DNA damage response element (mutS) were raised in a time-dependent fashion. K. pneumoniae showed high-level resistance to ciprofloxacin in the presence of mutations in QRDR and PMQR genes. Conclusion. The transcriptional response revealed the upregulation of DNA repair and protein folding elements (mutS and euTu) in ciprofloxacin stress and delayed cell division. The ciprofloxacin was found to trigger various stress responses in a time- and concentration-dependent manner.

The emergence of carbapenem-resistant bacterial pathogens is a significant and mounting health concern across the globe. At present, carbapenem resistance (CR) is considered as one of the most concerning resistance mechanisms and mainly found in gram-negative bacteria of the Enterobacteriaceae family. Although carbapenem resistance has been recognized in Enterobacteriaceae from last 20 years or so, recently it emerged as a global health issue as CR clonal dissemination of various Enterobacteriaceae members especially E. coli, and Klebsiella pneumoniae are reported from across the globe at an alarming rate. Phenotypically, carbapenems resistance is in due to the two key mechanisms, like structural mutation coupled with β-lactamase production and the ability of the pathogen to produce carbapenemases which ultimately hydrolyze the carbapenem. Additionally, penicillin-binding protein modification and efflux pumps are also responsible for the development of carbapenem resistance. Carbapenemases are classified into different classes which include Ambler classes A, B, and D. Several mobile genetic elements (MGEs) have their potential role in carbapenem resistance like Tn4401, Class I integrons, IncFIIK2, IncF1A, and IncI2. Taking together, resistance against carbapenems is continuously evolving and posing a significant health threat to the community. Variable mechanisms that are associated with carbapenem resistance, different MGEs, and supplementary mechanisms of antibiotic resistance in association with virulence factors are expanding day by day. Timely demonstration of this global health concern by using molecular tools, epidemiological investigations, and screening may permit the suitable measures to control this public health menace.

Caesalpinia bonduc has been used in herbal medicines for the treatment of a wide range of diseases from decades. The present study has explored the remedial potential and underlying mechanism of polyphenol extract of Caesalpinia bonduc in alloxanized diabetic rats. HPLC/MS analysis confirmed the presence of phenolics in considerable concentrations in Caesalpinia bonduc extract. Administration of different doses (250 and 500 mg/kg) of CPP extract to hyperglycemic rats for 8 weeks restored blood and serum glucose, insulin, glycosylated hemoglobin, leptin, amylin, and carbohydrate metabolizing enzymes level towards normal compared to alloxanized diabetic group. The effect of CPP extract on various genes such as Pdx-1, Ins-1, ngn-3, GLUT-4, and IRS-1 in insulin signaling pathway and Traf-4, Traf-6, and Mapk-8 in MAPK downstream JNK cascade was examined through qRT-PCR to access the core molecular mechanism involved in CPP-induced recovery of diabetes. Results have revealed that CPP extract reduced oxidative stress in pancreaticβcells by restoring free radical scavenging potential, reducing the mRNA expression of Mapk-8, Traf-4, and Traf-6, and increasing the Pdx-1, Ins-1, ngn-3, GLUT-4, and IRS-1 expression ensuing regeneration ofβcells and subsequent insulin release from pancreas. The results obtained in this study recommend that CPP extract may be a promising therapeutic restorative agent in the treatment of diabetes mellitus.

Depression and anxiety are the most common disorders among all age groups. Several antidepressant drugs including benzodiazepine, antidepressant tricyclics, azapirone, noradrenaline reuptake inhibitors, serotonin selective reuptake inhibitors, serotonin, noradrenaline reuptake inhibitors, and monoamine oxidase inhibitors have been used to treat these psychiatric disorders. However, these antidepressants are generally synthetic agents and can cause a wide range of side effects. The potential efficacy of plant-derived alkaloids has been reviewed against various neurodegenerative diseases including Alzheimer’s disease, Huntington disease, Parkinson’s disease, schizophrenia, and epilepsy. However, data correlating the indole alkaloids and antidepressant activity are limited. Natural products, especially plants and the marine environment, are rich sources of potential new drugs. Plants possess a variety of indole alkaloids, and compounds that have an indole moiety are related to serotonin, which is a neurotransmitter that regulates brain function and cognition, which in turn alleviates anxiety, and ensures a good mood and happiness. The present review is a summary of the bioactive compounds from plants and marine sources that contain the indole moiety, which can serve as potent antidepressants. The prospects of naturally occurring as well as synthetic indole alkaloids for the amelioration of anxiety and depression-related disorders, structure-activity relationship, and their therapeutic prospects have been discussed.

Diabetes mellitus is a metabolic disorder associated with short term as well as long‐term undesirable complications caused by persistent hyperglycemia. Recently, there has been emerging evidence that natural foods and their bioactive compounds are the key contributors to the treatment of diabetes and associated complications. This study was designed to explore the therapeutic efficacy of a fish protein‐rich diet for managing diabetes and associated complications in the diabetic Wistar rat model. A high‐protein (HP) diet (45% and 55% fish protein rich in ω3 fatty acids) was given to alloxan‐induced diabetic rats for 28 days. Blood samples were collected for monitoring serum glucose, oxidative stress markers, lipid profile, kidney function markers, serum proteins, and liver function markers. Results indicated that there was a noteworthy control (p, Diet acquiring the key role in metabolic homeostasis and promoting health. A balanced diet based on type, amount, and macronutrients such as proteins, fats, and carbohydrates is vital for managing diabetes. Results revealed the protective and therapeutic efficacy of high‐protein diet (fish protein) in alloxan‐induced diabetic rat models through normalizing serum glucose concentration, oxidative stress, lipid profile, RFTs, and LFTs. Conclusively, our findings suggest that fish protein can be useful in the management of diabetes and associated complications by medical nutrition. However, further research studies are required to further elucidate its mode of action.

The advent of multidrug resistance among pathogenic bacteria is imperiling the worth of antibiotics, which have previously transformed medical sciences. The crisis of antimicrobial resistance has been ascribed to the misuse of these agents and due to unavailability of newer drugs attributable to exigent regulatory requirements and reduced financial inducements. Comprehensive efforts are needed to minimize the pace of resistance by studying emergent microorganisms, resistance mechanisms, and antimicrobial agents. Multidisciplinary approaches are required across health care settings as well as environment and agriculture sectors. Progressive alternate approaches including probiotics, antibodies, and vaccines have shown promising results in trials that suggest the role of these alternatives as preventive or adjunct therapies in future.

Purpose The purpose of this paper is to evaluate the prevalence and antibiograms of bacteria isolated from various fresh fruit juices at a local market in Faisalabad. Design/methodology/approach Fresh fruit juice samples (n=125) were randomly collected using aseptic technique. Each sample (10 mL) was serially diluted with 90 mL of sterile peptone water, from 1×10−1 to 1×10−5. Each dilution was then used to inoculate nutrient agar by surface spread plating. Aerobic colony counts (ACCs) were determined by colony counting. The isolates were sub-cultured on blood and MacConkey agar. Preliminary identification was achieved on the basis of colony morphology and culture characteristic, and confirmed by API® 20E, 20NE, and API® Staph testing. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer disk diffusion assay, per CLSI 2015 guidelines. Findings The mean ACC ranged from 2.0×106 CFU/mL to 4.93×106 CFU/mL, with the highest ACC determined for orange juice. Overall, 153 polymicrobial were identified in 125 samples; 103 of these were Gram-negative rods (GNR) and 28 were Gram-positive cocci (GPC). Escherichia coli (n=38), Klebsiella pneumoniae (n=32) and Pseudomonas aeruginosa (n=24) were the predominant GNR; Staphylococcus aureus (n=28) was the predominant GPC. Antibiogram analysis revealed that all GNR were resistant to ampicillin. However, most E. coli isolates were resistant to ceftazidime (72.4 percent of isolates), and ceftriaxone and cefepime (68.9 percent), while most K. pneumoniae isolates were resistant to cefepime (72 percent) and ceftriaxone (64 percent). All S. aureus isolates were resistant to penicillin, while most (64 percent) were resistant to piperacillin; the most effective drugs against bacteria were vancomycin and imipenem. Practical implications The findings suggest that the local government regulatory food and public health authorities should take immediate emergency measures. Appropriate surveillance studies and periodic monitoring of food items should be regularly performed to safeguard public health. Originality/value The current study revealed the prevalence of multidrug-resistant bacteria in freshly prepared fruit juices sold by local street vendors.

The discovery of antibiotics was hailed as a historic breakthrough for the human race in the fight against bacterial and malignant infections. However, in a very short time, owing to their acute and aggressive nature, bacteria have developed resistance against antibiotics and other chemotherapeutics agents. Potentially, this situation could again result in bacterial infection outbreaks. Metal and metal oxide nanoparticles have been proven as better alternatives; the combination of antibiotics and metal oxide nanoparticles was shown to decrease the toxicity and enhance the antibacterial, antiviral, and anticancer efficacy of the agents. This review provides a detailed view about the role of metal and metal oxide nanoparticles in the treatment of infections in conjunction with antibiotics, their modes of action, and synergism. In addition, the problems of multidrug resistance are addressed and will allow the development of a comprehensive, reliable, and rational treatment plan. It is expected that this comprehensive review will lead to new research opportunities, which should be helpful for future applications in biomedical science.

Objectives Acacia nilotica (A. nilotica) has been used in ayurvedic system of medicine for the treatment of numerous metabolic disorders from decades. Despite its wide usage in traditional medicine system, to our knowledge, little attention has been given to the mechanisms involved in therapeutic potential of A. nilotica. The pupose of our study was to understand the molecular and biochemical mechanisms involved in protective effect of A. nilotica polyphenol extract (A. nilotica PPE) on diabetes induced by alloxan monohydrate. Methods Total polyphenols and total flavonoids in A. nilotica PPE were determined using Folin-Ciocalteu method and Aluminiun Chloride colorimetric method respectively. HPLC analysis of A. nilotica PPE was performed to determine the phenolic contents. Antidiabetic potential of A. nilotica PPE was evaluated through biochemical (FBG, serum glucose, serum insulin, HbA1c, serum C-peptide), antioxidant defense markers, Intracellular ROS and lipid peroxidation measurements as well as histopathological analysis. qRT-PCR analysis was also executed to measure the expression level of numerous genes involved in insulin signaling cascade (Pdx-1, ngn-3, Ins-1, GLUT-4, IRS-1) and c-Jun N-terminal kinase (JNK) downstream cascade (MAPK-8, Traf-4 & Traf-6) to determine the main molecular mechanisms involved in antidiabetic potential of A. nilotica PPE. Results Results of the study have confirmed the presence of total polyphenolic (61.17 mg GAE/g) and total flavonoid (53.12 mg CE/g) contents in A. nilotica PPE. HPLC assay of A.nilotica PPE revealed the presence of quercitin, gallic acid, chlorogenic acid, Kaempferol and catechin. A. nilotica PPE significantly inverted the hyperglycemia by reducing the FBG, serum glucose, HbA1c levels and improving the insulin & C-peptide levels. A. nilotica PPE improved the antioxidant defense markers (SOD, CAT, GPx, GSH) and reduced the intracellular ROS and TBARS levels. Alloxan induced histological changes were also recovered in extract treated groups. A. nilotica PPE upregulated the expressions of Pdx-1, ngn-3, Ins-1, GLUT-4, IRS-1 and downregulated the expressions of MAPK-8, Traf-4 & Traf-6 genes. Conclusion In a nutshell, A. nilotica PPE can be used as a better therapeutic approach for the management of both type 1 and type 2 diabetes as it may improve the beta cells regeneration, biochemical indicators and reduce the cellular stress.

Artemisia parviflora Roxb.(Asteraceae) has medicinal properties. This study evaluates the gastroprotective potential of A. parviflora seeds against aspirin induced ulcers in albino rabbits.Thirty-six rabbits were randomly divided into 6 equal groups (n = 6). Group 1 was control; group 2 received aspirin for 14 days; group 3 received omeprazole + aspirin for 14 days; groups 4, 5, and 6 received A. parviflora seed powder 250, 500, and 750 mg/kg, respectively along with aspirin, for 14 days. Total oxidant status (TOS), totalantioxidant capacity (TAC), malondialdehyde (MDA), and catalase (CAT) were determined to check the gastric damage. Ulcer score, gastric volume, gastric pH, and total acid output was also measured to determine gastroprotective potential of A. parviflora. A. parviflora seed powder exhibit gastroprotective potential with significant reduction in the ulcer score, acid output, and gastric volume while the pH of gastric mucosa increases significantly at the dose of 750 mg/kg when compared to aspirin treated group. Biochemical analysis showed a significant increase in TAC and CAT activity while it showed significant decrease in the levels of TOS and MDA which indicate reduction in gastric damage.A. parviflora seed powder proved to be gastroprotective at 250, 500 and 750 mg/kg with gastric protection of 47.5, 58.1, and 73.5%, respectively. It also has potent antioxidant properties. Key words: Antiulcer, ulcer score, gastric volume, gastric pH.

Background The purpose of this study was to perform a meta-analysis assessing the efficacy and predictors of success of endoscopic therapy in the management of patients with pancreas divisum. Methods An electronic database search (PubMed and ScienceDirect) was performed for relevant studies. Studies were selected based on predefined criteria and data were extracted on patient population, follow up, endotherapy methods, success rates and complication rates. A random-effect model was used to pool the effect size across studies. Heterogeneity testing and publication bias assessment were performed. Multivariate regression analysis was performed to identify predictors of successful endoscopic therapy. Results Of 381 articles reviewed, 23 studies with 874 patients met the inclusion criteria. All were case series with suboptimal quality. Endoscopic therapy included minor papilla sphincterotomy, minor papilla sphincteroplasty and dorsal duct stenting. Mean follow-up duration was 37 months. The rate of “improvement” as defined by authors after endoscopic therapy varied significantly across studies, ranging from 31-96%: 589/874 patients were reported to have improved, corresponding to a pooled efficacy rate of 67.5% (95% confidence interval [CI] 0.610-0.734; P=0.0001). The pooled rate of pancreatitis after endoscopic retrograde cholangiopancreatography was 10.1% (95%CI 0.084-0.124; 2-sided P=0.0001). On subgroup analysis, patients with recurrent acute pancreatitis had better endoscopic outcomes (pooled efficacy rate 76%, 95%CI 0.712-0.803, P=0.0001). Dorsal duct stenting and longer follow up were the only parameters predictive of successful endotherapy. Significant heterogeneity was observed within and across studies. Conclusions Endoscopic efficacy in pancreas divisum is estimated at 67.5%. Available studies are of poor quality with significant heterogeneity. Comparative studies with rigorous methodology are needed. Keywords Pancreas divisum, endoscopic therapy, minor papilla sphincterotomy, meta-analysis, systematic review, recurrent acute pancreatitis, chronic pancreatitis Ann Gastroenterol 2017; 30 (5): 550-558