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Background: Typhoid fever is a fatal disease in humans that is caused by Salmonella typhi. S. typhi infections need immediate antibiotic therapy, and their extensive use has led to multidrug-resistant (MDR) pathogens. The use of bacteriophages is becoming a new way to treat these resistant bacteria. This research was directed to bacteriophage isolation against S. typhi and to determine phage-antibiotic synergism. Aims: To isolate bacteriophages targeting S. typhi, the causative agent of typhoid fever, and investigate their potential synergistic effects when combined with antibiotics. Study design: A cross-sectional study. Methods: The Widal test was positive; twenty diarrheal stool samples were taken, and for confirmation of S. typhi, different biochemical tests were performed. The disc-diffusion technique was used to determine antimicrobial resistance, and the double agar overlay method was used for bacteriophage isolation from sewage water against S. typhi. To test antibiotic-phage synergism, the S. typhi bacteria was treated by phages together with varying antibiotic concentrations. Results: Eleven samples were positive for S. typhi with black colonies on SS-agar. These were catalase and MR positive with alkali butt on TSI. Clear plaques were observed after the agar overlay. Isolated phages were stable at various pH and temperature levels. Synergism was observed on agar plate. The zone was enlarged when phages were combined with bacterial lawn culture and ciprofloxacin disk. Bacterial growth inhibition had a significant p-value of 0.03 in titration plates, with the phage-ciprofloxacin combination being more effective than the phage and antibiotic alone. Conclusion: The study highlights the synergistic effects of isolated bacteriophages with antibiotics, which are not only effective against S. typhi infection but also decrease antibiotic resistance. [ABSTRACT FROM AUTHOR]

Metastasis is the most devastating attribute of breast cancer (BC) that leads to high mortality. It is a complex process of tumor cell migration, invasion, and angiogenesis. In this study, we evaluated the effect of ERA on BC metastasis and BC progression in vivo. The transwell invasion/migration and wound healing assays showed that ERA treatment significantly reduced the invasion and migration of BC cell lines. The expression of mesenchymal (E-cadherin and N-cadherin), matrix metalloproteinases (MMP2, MMP9), and stemness markers (Oct3) were down-regulated by ERA. Furthermore, ERA down-regulated angiogenic chemokines (CXCL1/2/3, CXCL5, and CXCL12) expression in the highly metastatic MDA-MB-231 cell line. The clonogenic survival of BC cells was also reduced by ERA treatment. Strikingly, ERA prevented DMBA-induced tumor growth in Swiss albino mice as depicted by a high animal survival rate (84%) in the ERA group and histopathological analysis. Conclusively, this study revealed that ERA possesses anti-metastatic potential and also reduces the growth of BC in vivo. Moreover, the GC–MS data revealed the presence of biologically active compounds (Lupeol, Phytol, phytosterol) and some rare (9, 19-Cyclolanost) phyto metabolites in ERA extract. However, further studies are suggestive to identify and isolate the therapeutic agents from ERA to combat BC and metastasis. [ABSTRACT FROM AUTHOR]

Phytobioactive compounds are plant secondary metabolites and bioactive compounds abundantly present in medicinal plants and have remarkable therapeutic potential. Oxidative stress and antibiotic resistance are major causes of present‐day ailments such as diabetes, atherosclerosis, cardiovascular disorders, cancer, and inflammation. The data for this review were collected from Google Scholar, PubMed, Directory of Open Access Journals (DOAJ), and Science Direct by using keywords: "Medicinal plants, Phytobioactive compounds, Polyphenols, Alkaloids, Carotenoids etc." Several studies have reported the pharmacological and therapeutic potential of the phytobioactives. Polyphenols, alkaloids, terpenes, and polysaccharides isolated from medicinal plants showed remarkable antioxidant, anticancer, cytotoxic, anti‐inflammatory, cardioprotective, hepatoprotective, immunomodulatory, neuroprotective, and antidiabetic activities. This literature review was planned to provide comprehensive insight into the biopharmacological and therapeutic potential of phytobioactive compounds. The techniques used for the extraction and isolation of phytobioactive compounds, and bioassays required for their biological activities such as antioxidant, antimicrobial, anti‐inflammatory, and cytotoxic activities, have been discussed. Characterization techniques for the structural elucidation of phytobioactive compounds such as HPLC, TLC, FTIR, GC–MS/MS, and NMR have also been discussed. This review concludes that phytobioactive compounds may be used as potential alternative to synthetic compounds as therapeutic agents for the treatment of various diseases. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are endogenous polypeptides produced by multicellular organisms in order to protect a host from pathogenic microbes. AMPs are also defined as host defense peptides because of their essential role in constituting the innate immunity system. The major mechanism of actions against microbial pathogens is attributed to perturbation of cell membrane of pathogens. In addition to the antimicrobial function, AMPs also act as effector molecules in wound healing, inflammation, and immune activation. AMPs have been considered as a potential therapeutic source due to its different mechanism of actions and broad-spectrum properties in comparison with the conventionally used antibiotics. As a new generation antibiotic, the AMPs have considerable benefits. AMPs are receiving great attention as promising alternatives to conventional antibiotics to overcome the current drug resistance crisis. In this review, we describe the classes, structural information about AMPs and their therapeutic role as novel antibiotic agents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chicken interferon-α (chIFN-α) is an important antiviral cytokine and represents one of the first lines of the chicken's innate immune system. The current study is the first-ever report of chicken IFN (chIFN) production in Pakistan. In this study, we have used live and UV-irradiated Newcastle disease virus (NDV) to induce the expression of chIFN-α in chicken embryo fibroblast (CEF) cells. ChIFN-α was partially purified in a two-step protocol; ultracentrifugation followed by treatment with anti-chIFN-β antibodies. The purified chIFN-α was analysed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and the in vitro antiviral potential of chIFN-α was determined against the H9N2 avian influenza virus (AIV) via a cytopathic inhibition assay. The relative mRNA level of the IFN-stimulated genes (ISGs) in the IFN-stimulated CEF cells was measured at various time intervals by a quantitative polymerase chain reaction (qPCR). The stability of natural chIFN-α to the temperature, pH, and ultraviolet (UV) light was also determined. The in vivo therapeutic potential of chIFN-α was determined in 7-day-old broiler chickens challenged with AIV. We found that a higher chIFN-α expression level was induced by the UV-irradiated NDV in the CEF cells as compared to the live NDV. The UV-irradiated NDV induced the maximum IFN production in the CEF cells at 24 h post-infection. Two bands of 21 kDa on SDS-PAGE confirmed the presence of the chIFN-α protein. The cytopathic inhibition assay indicated the strong antiviral activity of chIFN-α against AIV. Our results of the stability analysis showed that chIFN-α was stable at a wide range of temperatures and pH levels. However, a little exposure to UV-light resulted in a significant loss of antiviral activity. We also observed that the antiviral activity of chIFN-α is related to the expression levels of the antiviral ISGs. The results of the in vivo study showed that the chIFN-α therapy via the oral route resulted in a significant improvement in the tracheal pathology of chickens challenged with AIV. In conclusion, we suggest that chIFN-α could be an important therapeutic tool to control avian influenza infection in poultry. [ABSTRACT FROM AUTHOR]

Starting from the end of 2019 the new SARs-CoV-2 virus, in the period of a few months, had spread to 210 countries and its territories. The Wuhan wild animal market, in Hubei province, China is considered the epicenter of this pandemic. WHO declared the name COVID-19 to designate the disease caused by the SARS-CoV-2 virus. It is the third coronavirus pandemic after SARS in 2002-2003 and MERS-CoV in 2012. Genome sequencing of this new COVID-19/SARS-CoV-2 virus shows slight genetic diversity when compared to other coronaviruses. Owing to its pathogenesis, and less known replication cycle, no universal antiviral treatment can be applied and vaccine preparation is still a larger challenge. The present article will highlight transmission, pandemic status, genetic diversity current antiviral therapy, and vaccine trials for COVID-19. [ABSTRACT FROM AUTHOR]

aima Muzammil,2 Nafeesa Yasmeen,4 Muhammad Aamir Aslam,3 Mohsin Khurshid,2 Muhammad Hidayat Rasool,2 Zulqarnain Baloch11Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, People's Republic of China; 2Department of Microbiology, Government College University Faisalabad, Faisalabad, Pakistan; 3Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad, Pakistan; 4College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, People's Republic of ChinaCorrespondence: Bilal Aslam; Zulqarnain Baloch Email drbilalaslam@gcuf.edu.pk; znbalooch@yahoo.com 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 blaNDM-1 was found in 92.3% (12/13) isolates followed by blaOXA-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]