Impact of Doxorubicin and Docetaxel on Immune Checkpoint Expression in Colorectal Cancer: Insights into Chemotherapy Resistance Mechanisms.

After chemotherapy, tumor cells tend to become more aggressive, making it challenging for natural and adaptive immune responses to fight them. This often results in recurrence and metastasis, leading to higher mortality rates. The purpose of this study is to discover the mechanisms that cause chemotherapy resistance, including altered expression of immune checkpoints, in a colorectal cancer cell line. We used conventional methods to culture the SW-1116 colorectal cancer cell line in this study. The MTT assay was used to determine the IC50 and efficacy of Docetaxel and Doxorubicin. After treatment, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to analyze PD-L1, CTLA-4, and VISTA gene expression in the SW-1116 cell line. The upregulation of VISTA expression showed a significant increase (p < 0.0001) in response to both chemotherapy agents. Moreover, the expression of CTLA-4 exhibited a remarkable level of significance (p < 0.0001), and PD-L1 expression also displayed notable significance (p < 0.0001). Chemotherapeutic agents heighten immune checkpoint gene expression, highlighting potential immune response pathway modulation.

Comparing proteome changes involved in biofilm formation by Streptococcus mutans after exposure to sucrose and starch.

Streptococcus mutans is a main organism of tooth infections including tooth decay and periodontitis. The aim of this study was to assess the influence of sucrose and starch on biofilm formation and proteome profile of S. mutans ATCC 35668 strain. The biofilm formation was assessed by microtiter plating method. Changes in bacterial proteins after exposure to sucrose and starch carbohydrates were analyzed using matrix-assisted laser desorption/ionization mass spectrometry. The biofilm formation of S. mutans was increased to 391.76% in 1% sucrose concentration, 165.76% in 1% starch, and 264.27% in the 0.5% sucrose plus 0.5% starch in comparison to biofilm formation in the media without sugars. The abundance of glutamines, adenylate kinase, and 50S ribosomal protein L29 was increased under exposure to sucrose. Upregulation of lactate utilization protein C, 5-hydroxybenzimidazole synthase BzaA, and 50S ribosomal protein L16 was formed under starch exposure. Ribosome-recycling factor, peptide chain release factor 1, and peptide methionine sulfoxide reductase MsrB were upregulated under exposure to sucrose in combination with starch. The results demonstrated that the carbohydrates increase microbial pathogenicity. In addition, sucrose and starch carbohydrates can induce biofilm formation of S. mutans via various mechanisms such as changes in the expression of special proteins.

Acute hepatitis (Non Hepa A-E) of unknown origin among pediatrics.

Several clusters and individual cases of acute hepatitis have been reported in the US, Europe and recently in Asia and Central America since October 2021. A laboratory investigation of the common viral hepatitis agents (HAV, HBV, HCV, HDV and HEV) yielded negative results prompting the use of the term "acute non HepA-E hepatitis" to describe this condition. As of 24 June of 2022, WHO have reported 920 probable cases of severe acute hepatitis of unknown origin among pediatrics in 33 countries in five WHO regions. Since the previous reports on 27 May 2022, 270 new probable cases have been increased, including from four new countries, some of whom were also found to be positive for SARS-CoV-2. All the patients showed symptoms such as vomiting, diarrhea, jaundice, and abdominal pain. The patients' liver enzymes were remarkably increased. No connection with SARS-CoV-2 or its vaccine has been found so far. However, the suspected cause is adenovirus, including its genomic variations, because its pathogenesis and laboratory investigations have been positively linked. Until further evidence emerges, hygiene precautions could be helpful to prevent its spread.

A Comprehensive Study on the Antimicrobial Properties of Resveratrol as an Alternative Therapy.

Resveratrol is a polyphenolic antioxidant whose possible health benefits include anticarcinogenic, antiaging, and antimicrobial properties that have gained significant attention. The compound is well accepted by individuals and has been commonly used as a nutraceutical in recent decades. Its widespread usage makes it essential to study as a single agent as well as in combination with traditional prescription antibiotics as regards to antimicrobial properties. Resveratrol demonstrates the action of antimicrobials against a remarkable bacterial diversity, viruses, and fungus. This report explains resveratrol as an all-natural antimicrobial representative. It may modify the bacterial virulence qualities resulting in decreased toxic substance production, biofilm inhibition, motility reduction, and quorum sensing disturbance. Moreover, in conjunction with standard antibiotics, resveratrol improves aminoglycoside efficacy versus Staphylococcus aureus, while it antagonizes the deadly function of fluoroquinolones against S. aureus and also Escherichia coli. The present study aimed to thoroughly review and study the antimicrobial potency of resveratrol, expected to help researchers pave the way for solving antimicrobial resistance.

Proteomic Applications in Antimicrobial Resistance and Clinical Microbiology Studies.

Sequences of the genomes of all-important bacterial pathogens of man, plants, and animals have been completed. Still, it is not enough to achieve complete information of all the mechanisms controlling the biological processes of an organism. Along with all advances in different proteomics technologies, proteomics has completed our knowledge of biological processes all around the world. Proteomics is a valuable technique to explain the complement of proteins in any organism. One of the fields that has been notably benefited from other systems approaches is bacterial pathogenesis. An emerging field is to use proteomics to examine the infectious agents in terms of, among many, the response the host and pathogen to the infection process, which leads to a deeper knowledge of the mechanisms of bacterial virulence. This trend also enables us to identify quantitative measurements for proteins extracted from microorganisms. The present review study is an attempt to summarize a variety of different proteomic techniques and advances. The significant applications in bacterial pathogenesis studies are also covered. Moreover, the areas where proteomics may lead the future studies are introduced.

Carbohydrate polymer-based silver nanocomposites: Recent progress in the antimicrobial wound dressings.

Wound healing is a dynamic and complex process which affects the quality of life in patients and annually causes high costs for the health system, worldwide. Polymers from natural origins such as polysaccharides have gained particular interest between researchers for wound dressing applications due to their abundance in nature, biocompatibility with human tissues, and ideal physicochemical properties. Aside from their supportive effect in wound care, polysaccharides and their derivatives can actively contribute to the healing process. Silver nanoparticles are widely used noble metal nanoparticles incorporated in wound dressings due to their low toxicity for human cells, naturally availability, and strong antimicrobial effects. In the present study, we will review the most frequently used polysaccharides in wound dressing procedure with silver or silver nanoparticles accommodated. The methods of synthesis, physicochemical properties, healing efficiencies, toxicity against human tissues, antibacterial and antifungal effects of each material will also be discussed.

AdeB efflux pump gene knockdown by mRNA mediated peptide nucleic acid in multidrug resistance Acinetobacter baumannii.

Multidrug-resistant Acinetobacter baumannii isolates cause critical problems in health-care environments. AdeABC is a resistance-nodulation-cell division (RND)-type multidrug efflux pump conferring resistance to clinically essential antibiotics in A. baumannii, such as ciprofloxacin. This study aimed to target adeB gene with antisense peptide nucleic acid (PNA) and investigate its effect on resistance to antibiotics. NCBI database was used to design appropriate PNA to target adeB gene, by connecting PNA to mRNA, the translation of mRNA can be prevented. Three clinical isolates and A. baumannii ATCC 17978 were treated with the designed PNA by electroporation and competence procedure. Minimum Inhibitory concentration (MIC) of ciprofloxacin, colistin, and tetracycline were determined by microbroth dilution method. In addition, the expression level of adeB gene was measured by quantitative real-time PCR (qRT-PCR). Isolates used in this study had mutations in gyrA and parC genes corresponding to resistance to ciprofloxacin. MIC of resistance to ciprofloxacin after treatment with PNA was reduced from 32 µg/ml to16 µg/ml in A. baumannii ATCC 17978 isolate. Susceptibility level of tetracycline, in the 2 clinical isolates was decreased from 64 µg/ml to 32 µg/ml and in the other isolate was reduced from 128 µg/ml to 64 µg/ml. The expression level of adeB gene was decreased in A. baumannii ATCC 17978 (P > 0.01) but not in clinical isolate (P = 0.107). Findings of the present study indicate overexpression of adeB efflux pump has extra effect on resistance to antibiotics in isolates with a defined mechanism of resistance. Antisense technology is a feasible technique to suppress the function of these genes, which may be further exploited to control multidrug-resistant isolates.

Preparation of biocompatible and biodegradable silk fibroin/chitin/silver nanoparticles 3D scaffolds as a bandage for antimicrobial wound dressing.

One of the most serious challenge in wound care is difficulty of the infection control in wound healing process. Wound dressings with antimicrobial effects are useful to minimize the bacterial infections of wounds. In this study a biocompatible and biodegradable silk fibroin/chitin nanocomposite scaffolds with various content of silver nanoparticles (0.001, 0.01, and 0.1%) were fabricated via freeze-drying method for successful wound dressing application. The nanocomposite scaffolds have biocompatibility with high antimicrobial effects, good mechanical properties, and high porosity. Furthermore, swelling and water uptake, blood clotting, and biodegradability were also investigated. The antimicrobial evaluation with both disc diffusion method and colony counts imply that nanocomposite scaffolds have high antimicrobial activity and could successfully inhibit the growth of E. coli, S. aureus, and C. albicans. Also proliferation, cell viability, and cell attachment with MTT assay and DAPI staining on nHFFF2 cell, have proved the cytocompatibility nature of the nanocomposite scaffolds. All results revealed that prepared nanocomposite scaffolds are good candidate for wound dressing and could be use in further in-vivo uses.