No relationship exists between PBP 2a amounts expressed in different MRSA strains obtained clinically and their β-lactam MIC values

After establishing a linear relationship between the amount of penicillinbinding protein (PBP) 2a and membrane proteins of methicillin-resistant Staphylococcus aureus (MRSA) COL by dot-blot analysis using an antibody against PBP 2a, we determined the PBP 2a quantities in membrane fractions prepared from 14 different MRSA cells. Methicillin-sensitive S. aureus ATCC 6538P was used as a quality control strain. The amounts of PBP 2a diverged among the strains, and no relationship to β-lactam MIC values were observed in the corresponding strains

The growing complexity of COVID-19 drug and vaccine candidates: challenges and critical transitions

COVID-19 has nowadays affected almost all our societies and global health systems. The latest deadly pandemic has heavily influenced both life and livelihood worldwide. SARS-CoV-2 is the causative organism of COVID-19, that is spreading and infecting significantly higher compared to other coronavirus, due to its constant mutation characteristics. At present although several extensive clinical trials are ongoing, neither approved drug therapy nor any vaccine are available to safely fight SARS-CoV-2. However, a progressive race among numerous research groups to discover a radical cure for the COVID-19 is under way. This review aims to provide an updated insight of the current research, development and trials on repurposing existing drugs and preventive intervention for COVID-19, along with the related issues, complexities and challenges, especially after the observed high transmissibility lately

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

Pancreatic cancer (PC) begins within the organ of the pancreas, which produces digestive enzymes, and is one of the formidable cancers for which appropriate treatment strategies are urgently needed. Autophagy occurs in the many chambers of PC tissue, including cancer cells, cancer-related fibroblasts, and immune cells, and can be fine-tuned by various promotive and suppressive signals. Consequently, the impacts of autophagy on pancreatic carcinogenesis and progression depend greatly on its stage and conditions. Autophagy inhibits the progress of preneoplastic damage during the initial phase. However, autophagy encourages tumor formation during the development phase. Several studies have reported that both a tumor-promoting and a tumor-suppressing function of autophagy in cancer that is likely cell-type dependent. However, autophagy is dispensable for pancreatic ductal adenocarcinoma (PDAC) growth, and clinical trials with autophagy inhibitors, either alone or in combination with other therapies, have had limited success. Autophagy’s dual mode of action makes it therapeutically challenging despite autophagy inhibitors providing increased longevity in medical studies, highlighting the need for a more rigorous review of current findings and more precise targeting strategies. Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC

Recent Update and Drug Target in Molecular and Pharmacological Insights into Autophagy Modulation in Cancer Treatment and Future Progress

Recent evidence suggests that autophagy is a governed catabolic framework enabling the recycling of nutrients from injured organelles and other cellular constituents via a lysosomal breakdown. This mechanism has been associated with the development of various pathologic conditions, including cancer and neurological disorders; however, recently updated studies have indicated that autophagy plays a dual role in cancer, acting as a cytoprotective or cytotoxic mechanism. Numerous preclinical and clinical investigations have shown that inhibiting autophagy enhances an anticancer medicine’s effectiveness in various malignancies. Autophagy antagonists, including chloroquine and hydroxychloroquine, have previously been authorized in clinical trials, encouraging the development of medication-combination therapies targeting the autophagic processes for cancer. In this review, we provide an update on the recent research examining the anticancer efficacy of combining drugs that activate cytoprotective autophagy with autophagy inhibitors. Additionally, we highlight the difficulties and progress toward using cytoprotective autophagy targeting as a cancer treatment strategy. Importantly, we must enable the use of suitable autophagy inhibitors and coadministration delivery systems in conjunction with anticancer agents. Therefore, this review briefly summarizes the general molecular process behind autophagy and its bifunctional role that is important in cancer suppression and in encouraging tumor growth and resistance to chemotherapy and metastasis regulation. We then emphasize how autophagy and cancer cells interacting with one another is a promising therapeutic target in cancer treatment

Recent Update and Drug Target in Molecular and Pharmacological Insights into Autophagy Modulation in Cancer Treatment and Future Progress

Recent evidence suggests that autophagy is a governed catabolic framework enabling the recycling of nutrients from injured organelles and other cellular constituents via a lysosomal breakdown. This mechanism has been associated with the development of various pathologic conditions, including cancer and neurological disorders; however, recently updated studies have indicated that autophagy plays a dual role in cancer, acting as a cytoprotective or cytotoxic mechanism. Numerous preclinical and clinical investigations have shown that inhibiting autophagy enhances an anticancer medicine’s effectiveness in various malignancies. Autophagy antagonists, including chloroquine and hydroxychloroquine, have previously been authorized in clinical trials, encouraging the development of medication-combination therapies targeting the autophagic processes for cancer. In this review, we provide an update on the recent research examining the anticancer efficacy of combining drugs that activate cytoprotective autophagy with autophagy inhibitors. Additionally, we highlight the difficulties and progress toward using cytoprotective autophagy targeting as a cancer treatment strategy. Importantly, we must enable the use of suitable autophagy inhibitors and coadministration delivery systems in conjunction with anticancer agents. Therefore, this review briefly summarizes the general molecular process behind autophagy and its bifunctional role that is important in cancer suppression and in encouraging tumor growth and resistance to chemotherapy and metastasis regulation. We then emphasize how autophagy and cancer cells interacting with one another is a promising therapeutic target in cancer treatment

Chitosan-Coated Polymeric Silver and Gold Nanoparticles: Biosynthesis, Characterization and Potential Antibacterial Applications: A Review

Biosynthesized metal nanoparticles, especially silver and gold nanoparticles, and their conjugates with biopolymers have immense potential in various fields of science due to their enormous applications, including biomedical applications. Polymeric nanoparticles are particles of small sizes from 1 nm to 1000 nm. Among different polymeric nanoparticles, chitosan-coated silver and gold nanoparticles have gained significant interest from researchers due to their various biomedical applications, such as anti-cancer, antibacterial, antiviral, antifungal, anti-inflammatory technologies, as well as targeted drug delivery, etc. Multidrug-resistant pathogenic bacteria have become a serious threat to public health day by day. Novel, effective, and safe antibacterial agents are required to control these multidrug-resistant pathogenic microorganisms. Chitosan-coated silver and gold nanoparticles could be effective and safe agents for controlling these pathogens. It is proven that both chitosan and silver or gold nanoparticles have strong antibacterial activity. By the conjugation of biopolymer chitosan with silver or gold nanoparticles, the stability and antibacterial efficacy against multidrug-resistant pathogenic bacteria will be increased significantly, as well as their toxicity in humans being decreased. In recent years, chitosan-coated silver and gold nanoparticles have been increasingly investigated due to their potential applications in nanomedicine. This review discusses the biologically facile, rapid, and ecofriendly synthesis of chitosan-coated silver and gold nanoparticles; their characterization; and potential antibacterial applications against multidrug-resistant pathogenic bacteria

Phylogenetic diversity and functional potential of large and cell-associated viruses in the Bay of Bengal

ABSTRACT The Bay of Bengal (BoB) is the world’s largest bay, offering essential services like fishing and recreation while holding significant economic value for coastal communities. However, the BoB faces environmental challenges from monsoons, freshwater inputs, rising sea levels, and intensified cyclones due to climate change. Human activities such as tourism and development also impact the region, necessitating a global change perspective. Despite its importance, microbial diversity and ecology in the BoB remain largely unexplored. We focused on large and cell-associated viruses (i.e., originating from the cellular size fraction), particularly giant viruses and large phages in two BoB coastal sites: Cox’s Bazar, a populated beach with freshwater influences, and Saint Martin Island, a less affected resort island. Metagenomic sequencing reveals a higher abundance and diversity of viruses in Cox’s Bazar and presence of viruses that suggest freshwater intrusion and runoff. We identified 1962 putative phage genomes (10–655 kbp). Notably, 16 “large” phages >100 kbp were found in Saint Martin, and a terminase large subunit marker gene phylogeny revealed substantial diversity of large phages along the BoB coast. The BoB virome encodes diverse functionalities, with a greater presence of auxiliary metabolic genes in the Cox’s Bazar viral community. Additionally, five giant virus genomes (phylum Nucleocytoviricota) encoding various functionalities are reconstructed from Cox’s Bazar (83–876 kbp). This pioneering study revealing the viral diversity and host interactions in coastal BoB lays the foundation for future investigations into viral impact on biogeochemical cycles and the microbial food web in this understudied environment. IMPORTANCE The BoB, the world’s largest bay, is of significant economic importance to surrounding countries, particularly Bangladesh, which heavily relies on its coastal resources. Concurrently, the BoB holds substantial ecological relevance due to the region’s high vulnerability to climate change-induced impacts. Yet, our understanding of the BoB’s microbiome in relation to marine food web and biogeochemical cycling remains limited. Particularly, there are little or no data on the viral diversity and host association in the BoB. We examined the viral community in two distinct BoB coastal regions to reveal a multitude of viral species interacting with a wide range of microbial hosts, some of which play key roles in coastal biogeochemical cycling or potential pathogens. Furthermore, we demonstrate that the BoB coast harbors a diverse community of large and giant viruses, underscoring the importance of investigating understudied environments to discover novel viral lineages with complex metabolic capacities. The BoB, the world’s largest bay, is of significant economic importance to surrounding countries, particularly Bangladesh, which heavily relies on its coastal resources. Concurrently, the BoB holds substantial ecological relevance due to the region’s high vulnerability to climate change-induced impacts. Yet, our understanding of the BoB’s microbiome in relation to marine food web and biogeochemical cycling remains limited. Particularly, there are little or no data on the viral diversity and host association in the BoB. We examined the viral community in two distinct BoB coastal regions to reveal a multitude of viral species interacting with a wide range of microbial hosts, some of which play key roles in coastal biogeochemical cycling or potential pathogens. Furthermore, we demonstrate that the BoB coast harbors a diverse community of large and giant viruses, underscoring the importance of investigating understudied environments to discover novel viral lineages with complex metabolic capacities