Comparison of Creatine Kinase-MB, Troponin-I, Troponin-T, Triiodothyronine, Thyroxine, Apoprotein-B and Homocysteine between Non-smokers, Smokers at High Altitudes, and Smokers at Sea Level.

Earlier diagnosis of heart disease can occur via awareness of biochemical changes. Keeping this in view, we wanted to determine if there was any difference between biochemical heart parameters between non-smokers (the control group), smokers who live at a high altitude, or smokers who live at sea level. There were 180 participants categorised into three groups, A, B, and C, depending upon their smoking/non-smoking classification, or distance from sea level. Blood samples were taken as per requirements to check levels of creatine kinase-MB, troponin-I, troponin-T, Triiodothyronine (T3), Thyroxine (T4), Apolipoprotein B (apo-B), and homocysteine, and subjected to enzyme-linked immunoassay (ELISA) investigations. Creatine kinase-MB, troponin-I, troponin-T, T3, thyroxine, apoprotein-B, and homocysteine all exhibited a noteworthy difference (p≤0.01) when compared between non-smokers and smokers (either at a high altitude or sea level), but only troponin I and T3 showed a noteworthy difference when compared between smokers at a high altitude versus at sea level (p≤0.01) as follows: Creatine kinase-MB, p=0.434; troponin-I, troponin-T, p=0.208; T3, p≤0.01; thyroxine, p=0.190; apoprotein-B, p=0.008; and homocysteine, p=0.039. It has been found that significant differences exist between smokers and non-smokers regarding cardiovascular (CV) pathology, whether the person resides at a high altitude or sea level. However, additional studies should be performed to find the correlation between smokers at a high altitude versus and smokers at sea level, which can change the treatment methods at high altitudes and pave the way for finding new medicines.

Phytosomes: A promising delivery system for anticancer agents by using phytochemicals in cancer therapy.

Plant extracts have been shown to be effective in treating a variety of ailments; however their hydrophilic nature and unique chemical structure have caused significant hurdles due to their low bioavailability. Phytosomes technology is used to improve the absorption of phytoconstituents that are difficult to absorb. Among the leading deaths in the society is malignancy. The aforementioned consumes remained a big issue for modern chemotherapy since it has yet to be treated in an efficient manner. The goal of this study is to outline the most recent research on the potential use of phytosome complexes for cancer therapy, as well as the formulation processes and mechanism of transportation through phytosomes.Nanotechnology has paved the way for cancer therapy by altering key features of medications and their carriers. Novel drug delivery systems are used to transfer antitumor drugs to the particular site via different nanostructures. Among several unique drug delivery systems, phytosomes are a creative way to transfer phytoactive compounds to the site of action, and several phytosomes formulations are now being used in clinical settings. Phytoconstituents' anti-cancer activities are increased by phytosomal formulations.

Klebsiella oxytoca: an efficient pyrene-degrading bacterial strain isolated from petroleum-contaminated soil.

Polycyclic aromatic hydrocarbons (PAHs) are the hazardous xenobiotic agents of oil production. One of the methods to eliminate hazardous compounds is bioremediation, which is the most efficient and cost-effective method to eliminate the harmful byproducts of crude petroleum processing. In this study, five pure bacterial isolates were isolated from petroleum-contaminated soil, four of which showed a robust growth on the PAH pyrene, as a sole carbon source. Various methods viz mass spectroscopy, biochemical assays, and 16S RNA sequencing employed to identify the isolates ascertained the consistent identification of Klebsiella oxytoca by all three methods. Scanning electron microscopy and Gram staining further demonstrated the characterization of the K. oxytoca. High-performance liquid chromatography of the culture supernatant of K. oxytoca grown in pyrene containing media showed that the cells started utilizing pyrene from the 6th day onwards and by the 12th day of growth, 70% of the pyrene was completely degraded. A genome search for the genes predicted to be involved in pyrene degradation using Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed their presence in the genome of K. oxytoca. These results suggest that K. oxytoca would be a suitable candidate for removing soil aromatic hydrocarbons.

Detection of chikungunya virus in the Southern region, Saudi Arabia.

BACKGROUND AND AIM: Despite the fact that the chikungunya viral infection is a neglected disease, complications such as hemorrhagic fever, arthritis, and lymphopenia remain a health concern. The aim of this study was to determine the prevalence of the chikungunya virus in the Southern Region, Saudi Arabia. Enzyme immunoassay and polymerase chain reaction have been compared between samples. MATERIALS AND METHODS: Forty samples from two southern hospitals in Saudi Arabia were collected between December 2019 and February 2020 and screened for chikungunya virus IgG antibodies and for viral RNA. Selection criteria were based on hematological parameters and rheumatological profiles such as rheumatoid factor, c-reactive protein, anti-nuclear antibody, and anti-cyclic citrullinated peptide (anti-CCP) of out-patients. RESULTS: One confirmed case of chikungunya virus was detected using the ELISA test. However, no viral RNA was detected in any of the samples. This suggests that the virus is cleared rapidly in patients. CONCLUSION: Chikungunya is a neglected viral disease in Saudi Arabia. Future work should focus on detailed investigation of this viral infection and its vectors.

Green synthesis of mono and bimetallic alloy nanoparticles of gold and silver using aqueous extract of Chlorella acidophile for potential applications in sensors.

Bimetallic or alloy nanoparticles (NPs) have improved properties compared to their monometallic forms. Microalgae being rich in biocompatible reductants and being ecofriendly are potential sources to synthesize fuctionalized NPs. In this study, biosynthesis of silver, gold, and bimetallic NPs was carried out via bioreduction using aqueous extract of algal isolate Chlorella acidophile, inhabitant of non-arable land. C. acidophile is known to contain highly bioactive functional moieties, which can serve as nanobiofactories for metallic NPs. Various characterization techniques viz, UV-visible spectrophotometer, X-ray diffraction analysis, X-ray photo-electron spectroscopy, and Raman spectroscopy were employed to determine their composition, structure, and crystal phase. The monometallic and bimetallic particles were found to be crystalline state and generally in a spherical shape. Their size ranged from 5 to 45 nm and the corresponding FTIR spectra indicated that the specific organic functional groups from algal extract were involved in the bio-reduction. Furthermore, the core-shell in the case of Au-Ag NPs was formed due to the simultaneous reduction of gold and silver ions. An enhanced and more pronounced Raman spectra of Au-Ag NP compared to individual Au NP indicated the improved properties of bimetallic NPs, the latter having been of immense potential to be used as sensors in industries.

Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape.

RNA-seq technologies have provided significant insight into the transcription networks of mycobacteria. However, such studies provide no definitive information on the translational landscape. Here, we use a combination of high-throughput transcriptome and proteome-profiling approaches to more rigorously understand protein expression in two mycobacterial species. RNA-seq and ribosome profiling in Mycobacterium smegmatis, and transcription start site (TSS) mapping and N-terminal peptide mass spectrometry in Mycobacterium tuberculosis, provide complementary, empirical datasets to examine the congruence of transcription and translation in the Mycobacterium genus. We find that nearly one-quarter of mycobacterial transcripts are leaderless, lacking a 5' untranslated region (UTR) and Shine-Dalgarno ribosome-binding site. Our data indicate that leaderless translation is a major feature of mycobacterial genomes and is comparably robust to leadered initiation. Using translational reporters to systematically probe the cis-sequence requirements of leaderless translation initiation in mycobacteria, we find that an ATG or GTG at the mRNA 5' end is both necessary and sufficient. This criterion, together with our ribosome occupancy data, suggests that mycobacteria encode hundreds of small, unannotated proteins at the 5' ends of transcripts. The conservation of small proteins in both mycobacterial species tested suggests that some play important roles in mycobacterial physiology. Our translational-reporter system further indicates that mycobacterial leadered translation initiation requires a Shine Dalgarno site in the 5' UTR and that ATG, GTG, TTG, and ATT codons can robustly initiate translation. Our combined approaches provide the first comprehensive view of mycobacterial gene structures and their non-canonical mechanisms of protein expression.

Comparative study of Mirs(') (Mushtaq and Shabir) technique of prepuce preserving minimally invasive urethroplasty with Snodgrass urethroplasty for repair of distal hypospadias without chordee A prospective study.

BACKGROUND: There is no single, universally applicable technique for hypospadias repair and numerous techniques have been practised from time to time. We compare the results of our new technique (Mirs' technique also called Mush & Shab's technique) to Snodgross urethroplasty. Mirs' technique is a modified version of Thiersch-Duplay urethroplasty. MATERIAL AND METHODS: This prospective comparative study was carried out in a tertiary care hospital of Northern India over a period of 3 years from March 2010 to March 2013 and included 120 patients of anterior (distal penile, subcoronal, coronal and glanular) hypospadias without chordee. They underwent either Mirs' technique (group 1 n = 60) or Snodgrass technique (group 2 n = 60). Follow-up was at 1-week, 1-month, 3 months and 6 months. RESULTS: The mean operative time was 55 min (range: 43-70 min) in group 1 and 71.9 min (range: 60-81 min) in group 2 (P < 0.001). Urethrocutaneous fistula developed in two and four patients in group 1 and 2, respectively. Fistula closure was done at least 3 months postoperatively, and there was no significant difference in success rate between the two groups. Three cases of glanular dehiscence were detected (one in group 1 and two in group 2); the patient from group 1 had a successful repair using the already preserved prepuce. CONCLUSION: Mirs' modification of Thiersch-Duplay technique for distal hypospadias is a time saving procedure with a lower overall complication rate. Valuable local tissue is preserved to deal with any complication that may occur. Analgesic requirement was significantly lower in this minimally traumatic technique. As it is less time consuming, simple and easy to learn with a short learning curve, this technique deserves application in cases of distal hypospadias.

Mycobacterial gene cuvA is required for optimal nutrient utilization and virulence.

To persist and cause disease in the host, Mycobacterium tuberculosis must adapt to its environment during infection. Adaptations include changes in nutrient utilization and alterations in growth rate. M. tuberculosis Rv1422 is a conserved gene of unknown function that was found in a genetic screen to interact with the mce4 cholesterol uptake locus. The Rv1422 protein is phosphorylated by the M. tuberculosis Ser/Thr kinases PknA and PknB, which regulate cell growth and cell wall synthesis. Bacillus subtilis strains lacking the Rv1422 homologue yvcK grow poorly on several carbon sources, and yvcK is required for proper localization of peptidoglycan synthesis. Here we show that Mycobacterium smegmatis and M. tuberculosis strains lacking Rv1422 have growth defects in minimal medium containing limiting amounts of several different carbon sources. These strains also have morphological abnormalities, including shortened and bulging cells, suggesting a cell wall defect. In both mycobacterial species, the Rv1422 protein localizes uniquely to the growing cell pole, the site of peptidoglycan synthesis in mycobacteria. An M. tuberculosis ΔRv1422 strain is markedly attenuated for virulence in a mouse infection model, where it elicits decreased inflammation in the lungs and shows impaired bacterial persistence. These findings led us to name this gene cuvA (carbon utilization and virulence protein A) and to suggest a model in which deletion of cuvA leads to changes in nutrient uptake and/or metabolism that affect cell wall structure, morphology, and virulence. Its role in virulence suggests that CuvA may be a useful target for novel inhibitors of M. tuberculosis during infection.

Synthesis, biological profile and computational insights of new derivatives of benzo [B][1,4] diazepines as prospective anticancer agents for inhibiting the CDK-2 protein.

In the current work, a new series of benzo[b][1, 4] diazepines (A-1 to C-4) was synthesized and screened against three different human cancer cell lines, HepG2 (hepatocellular carcinoma), HeLa (cervical cancer) and MCF-7 (breast cancer), by employing MTT (MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. The outcomes of in vitro screening revealed that all the compounds exhibited momentous anticancer activity, most notably against the MCF-7 cell line by B1-4 compounds. Further, network pharmacology, UALCAN analysis, molecular docking, molecular dynamics (MD) simulations and density functional theory calculations were conducted to explore expression analysis, pharmacokinetics, toxicity profiles and binding interactions of the B1-4 compounds. By UALCAN, we explored the expression analysis of CDK-2 in 19 cancers. Through UALCAN, Pan-cancer analysis revealed that the expression of CDK-2 in 19 cancers was statistically significant. Among the 19 cancers, the CDK-2 expression was significantly upregulated in breast cancer (BRCA), cervical cancer (CESC) and lung carcinoma (LUSC) than normal tissues. Enzyme-docking examination revealed that B1-4 compounds exhibited significant binding affinity against the CDK-2 (PDB ID: 5IEV) drug target protein. Furthermore, MD simulations supported the docking results, which confirmed that the ligand + protein complex was in a stable conformation throughout the simulation time of 100 nanoseconds. Therefore, the present study demonstrates the potential of these benzo [b][1,4] diazepines as promising drug candidates against cancer.Communicated by Ramaswamy H. Sarma.

A new series of benzodiazepine molecules were designed and synthesized as CDK-2 inhibitors.In vitro anticancer potential against HepG2, HeLa and MCF-7 cancer cells were assessed.Network pharmacology; expression analysis; in silico docking; molecular dynamics simulation; molecular mechanics­generalized Born and surface area; and absorption, distribution, metabolism, excretion and toxicity studies were carried out.This study overall revealed the anticancer activity of benzodiazepines by integrating network pharmacology, molecular modeling and in vitro experiments.

Antimycobacterial and Anticancer Properties of Myrtus communis Leaf Extract.

BACKGROUND: Plant-derived products or extracts are widely used in folk/traditional medicine to treat several infections, ailments, or disorders. A well-known medicinal herb, Myrtus communis is an evergreen fragrant plant native to the Mediterranean region that has been used for ages in traditional medicine around the world. MATERIALS AND METHODS: The microplate alamarBlue assay and the well diffusion method were used to evaluate the zone of inhibition and MIC, respectively. The double-disc diffusion method was used to investigate the synergy between antibiotics and the extract. The crystal violet method was used to investigate biofilm development. The SulphoRhodamine-B assay and DNA flow cytometry were used to investigate the proliferation and subsequent distribution of cells among different phases of the cell cycle. The apoptotic and necrotic phases of the cancer cells were examined using flow cytometry in conjunction with Annexin V-FITC/PI labeling. Using the IBM SPSS statistical program, a one-way ANOVA with Tukey's post hoc test was employed for statistical analysis. RESULTS: The ethanolic leaf extract of M. communis showed a strong growth inhibition effect (zone of inhibition: 20.3 ± 1.1-26.3 ± 2.5 mm, MIC: 4.88-312.5 µg/mL, and MBC: 39.07-1250 µg/mL) against several rapidly growing and slow-growing mycobacterial strains in a dose-dependent manner. Damage to the cell wall of bacterial cells was determined to be the cause of the antimycobacterial action. The extract inhibited biofilm formation (MBIC of 9.7 µg/mL) and eradicated already-formed mature and ultra-mature biofilms of M. smegmatis, with MBEC values of 78 µg/mL and 156 µg/mL, respectively. Additionally, the extract exhibited potent anticancer effects against diverse cancer cell lines of the breast (MCF-7), liver (HepG2), cervix (HeLa), and colon (HCT116) (IC50 for HCT116: 83 ± 2.5, HepG2: 53.3 ± 0.6, MCF-7: 41.5 ± 0.6, and HeLa: 33.3 ± 3.6) by apoptosis after arresting the cells in the G1 phase of the cell cycle. CONCLUSIONS: These results suggest that M. communis leaf extract is a potential source of secondary metabolites that could be further developed as potential anticancer and antimycobacterial agents to treat diverse types of cancers and mycobacterial infections.

Network pharmacology and experimental insights into STAT3 inhibition by novel isoxazole derivatives of piperic acid in triple negative breast cancer.

STAT3 is a crucial member within a family of seven essential transcription factors. Elevated STAT3 levels have been identified in various cancer types, notably in breast cancer (BC). Consequently, inhibiting STAT3 is recognized as a promising and effective strategy for therapeutic intervention against breast cancer. We herein synthesize a library of isoxazole (PAIs) from piperic acid [2E, 4E)-5-(2H-1,3-Benzodioxol-5-yl) penta-2,4-dienoic acid] on treatment with propargyl bromide followed by oxime under prescribed reaction conditions. Piperic acid was obtained by hydrolysis of piperine extracted from Piper nigrum. First, we checked the binding potential of isoxazole derivatives with breast cancer target proteins by network pharmacology, molecular docking, molecular dynamic (MD) simulation and cytotoxicity analysis as potential anti-breast cancer (BC) agents. The multi-source databases were used to identify possible targets for isoxazole derivatives. A network of protein-protein interactions (PPIs) was generated by obtaining 877 target genes that overlapped gene symbols associated with isoxazole derivatives and BC. Molecular docking and MD modelling demonstrated a strong affinity between isoxazole derivatives and essential target genes. Further, the cell viability studies of isoxazole derivatives on the human breast carcinoma cell lines showed toxicity in all breast cancer cell lines. In summary, our study indicated that the isoxazole derivative showed the significant anticancer activity. The results highlight the prospective utility of isoxazole derivatives as new drug candidates for anticancer chemotherapy, suggesting route for the continued exploration and development of drugs suitable for clinical applications.

The extracytoplasmic domain of the Mycobacterium tuberculosis Ser/Thr kinase PknB binds specific muropeptides and is required for PknB localization.

The Mycobacterium tuberculosis Ser/Thr kinase PknB has been implicated in the regulation of cell growth and morphology in this organism. The extracytoplasmic domain of this membrane protein comprises four penicillin binding protein and Ser/Thr kinase associated (PASTA) domains, which are predicted to bind stem peptides of peptidoglycan. Using a comprehensive library of synthetic muropeptides, we demonstrate that the extracytoplasmic domain of PknB binds muropeptides in a manner dependent on the presence of specific amino acids at the second and third positions of the stem peptide, and on the presence of the sugar moiety N-acetylmuramic acid linked to the peptide. We further show that PknB localizes strongly to the mid-cell and also to the cell poles, and that the extracytoplasmic domain is required for PknB localization. In contrast to strong growth stimulation by conditioned medium, we observe no growth stimulation of M. tuberculosis by a synthetic muropeptide with high affinity for the PknB PASTAs. We do find a moderate effect of a high affinity peptide on resuscitation of dormant cells. While the PASTA domains of PknB may play a role in stimulating growth by binding exogenous peptidoglycan fragments, our data indicate that a major function of these domains is for proper PknB localization, likely through binding of peptidoglycan fragments produced locally at the mid-cell and the cell poles. These data suggest a model in which PknB is targeted to the sites of peptidoglycan turnover to regulate cell growth and cell division.

Antibacterial and Antibiofilm Activities of ß-Lapachone by Modulating the Catalase Enzyme.

BACKGROUND: Bacterial infections constantly have a large impact on public health, because of increased rates of resistance and reduced frequency of development of novel antibiotics. The utility of conventional antibiotics for treating bacterial infections has become increasingly challenging. The aim of the study was to assess the antibacterial effect of ß-Lapachone (ß-Lap), a novel synthetic compound. METHODS: The antibacterial activity of the ß-Lap compound was examined against laboratory strains by agar well diffusion method and broth dilution assay. Growth kinetics in presence of ß-Lap on Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa (ATCC 27853) were assessed by microplate alamarBlue assay. Crystal violet blue assay was used for biofilm inhibition and biofilm eradication. P. aeruginosa catalase (KatA) complexed with ß-Lap was modeled using molecular docking approach. RESULTS: ß-Lap exhibited potent antimicrobial activity against laboratory strains of bacteria with MIC of 0.2 mM for S. saprophyticus and Staphylococcus aureus, and 0.04 mM for Staphylococcus epidermidis and Pseudomonas aeruginosa ATCC 27853. The inhibition of catalase enzyme was found to be the cause for its antibacterial activity. Bioinformatics analysis suggests that ß-Lap can inhibit KatA activity by interacting with catalase proximal active site and heme binding site. The activity of some commercial antibiotics was enhanced in association with ß-Lap. In addition, ß-Lap inhibited the biofilm formation and eradicated the already formed and ultra-mature biofilms of aforesaid bacterial strains. CONCLUSION: These observations indicated that ß-Lap could be a promising antibacterial agent for the treatment and prevention of infectious diseases.

Design, synthesis, and unraveling the antibacterial and antibiofilm potential of 2-azidobenzothiazoles: insights from a comprehensive in vitro study.

The present study reports the synthesis of 2-azidobenzothiazoles from substituted 2-aminobenzothiazoles using sodium nitrite and sodium azide under mild conditions. All the synthesized compounds were examined for their antibacterial activity against Gram (+) bacteria, Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 51299), Bacillus cereus (ATCC 10876) and Gram (-) bacteria, Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 10145), Klebsiella pneumonia (ATCC BAA-2146)and clinical isolates of Gram (+) Methicillin Resistant S. aureus (MRSA) and Multi Drug Resistant E. coli. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values by broth dilution method revealed that compound 2d exhibited significant antibacterial potential against E. faecalis and S. aureus with MIC of 8 µg/mL, while other synthesized compounds had only moderate effects against all the tested species. The compound significantly inhibited the biofilm formation of the bacterial strains below its MIC. The selective cytotoxicity of Compound 2d towards bacterial cells was evidenced on extended exposure of Human Embryonic Kidney-293 cell line to higher concentrations of the compound. Hence, the present study confirmed that compound 2d can be a potential drug candidate for future development as an antibacterial drug.

Therapeutic approaches for chronic hepatitis C: a concise review.

Hepatitis C virus (HCV) infection is a significant global health concern, prompting the need for effective treatment strategies. This in-depth review critically assesses the landscape of HCV treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal in HCV management and herbal approaches rooted in traditional and complementary medicine. Advancements in therapeutic development and enhanced clinical outcomes axis on a comprehensive understanding of the diverse HCV genome, its natural variations, pathogenesis, and the impact of dietary, social, environmental, and economic factors. A thorough analysis was conducted through reputable sources such as Science Direct, PubMed, Scopus, Web of Science, books, and dissertations. This review primarily focuses on the intricate nature of HCV genomes and explores the potential of botanical drugs in both preventing and treating HCV infections.

Artificial intelligence and cheminformatics tools: a contribution to the drug development and chemical science.

In the ever-evolving field of drug discovery, the integration of Artificial Intelligence (AI) and Machine Learning (ML) with cheminformatics has proven to be a powerful combination. Cheminformatics, which combines the principles of computer science and chemistry, is used to extract chemical information and search compound databases, while the application of AI and ML allows for the identification of potential hit compounds, optimization of synthesis routes, and prediction of drug efficacy and toxicity. This collaborative approach has led to the discovery, preclinical evaluations and approval of over 70 drugs in recent years. To aid researchers in the pursuit of new drugs, this article presents a comprehensive list of databases, datasets, predictive and generative models, scoring functions and web platforms that have been launched between 2021 and 2022. These resources provide a wealth of information and tools for computer-assisted drug development, and are a valuable asset for those working in the field of cheminformatics. Overall, the integration of AI, ML and cheminformatics has greatly advanced the drug discovery process and continues to hold great potential for the future. As new resources and technologies become available, we can expect to see even more groundbreaking discoveries and advancements in these fields.Communicated by Ramaswamy H. Sarma.

Prevalence of Clostridium Difficile Infection (CDI) among Inflammatory Bowel Disease (IBD) Patients in Comparison to Non-IBD Patients in King Abdulaziz Medical City in Jeddah.

Background: The prevalence of Clostridium difficile infection (CDI) as a common complication among inflammatory bowel disease (IBD) has been reported to increase worldwide and has been associated with a poor IBD outcome. Objectives: In this study, our aim was to report on the prevalence of CDI among IBD vs. non-IBD patients in King Abdulaziz Medical City (KAMC). Methods: This retrospective descriptive study was carried out between 2016 and 2020. Data of 89 patients reported with CDI in KAMC were analyzed for demographics and correlations between various characteristics such as BMI, personal/family history of IBD, infection with CDI, diagnosis, method of diagnosis, and treatment modalities. Results: Of the total 89 CDI patients, 59 (66.3%) were adults and 30 (33.7%) were pediatric, of which 36 (40.4%) were females and 53 (59.6%) were males. PCR was the main method of choice for the diagnosis of CDI (89.9%) followed by a positive-culture result (10.0%). Seventy-eight (87.6%) CDI patients were found to be immunocompromised, with two patients diagnosed with IBDs, one with UC, and one with CD. The recurrence rate was 38.4 (30 patients) among the immunocompromised group in comparison to 27.2 (3 patients) in the immunocompetent group (p=0.584). Conclusion: In this study, we found that adults were more prone to CDI infection, especially within hospital settings, and most of the CDI infections occurred in immunocompromised individuals, with cancer as the most common cause of it.

Design-of-Experiment-Assisted Fabrication of Biodegradable Polymeric Nanoparticles: In Vitro Characterization, Biological Activity, and In Vivo Assessment.

Berberine (BER) is an alkaloid obtained from berberis plant having broad biological activities including anticancer. BER-encapsulated alginate (ALG)/chitosan (CHS) nanoparticles (BER-ALG/CHS-NPs) were developed for long-acting improved treatment in breast cancer. The surface of the NPs was activated by a conjugation reaction, and thereafter, the BER-ALG/CHS-NP surface was grafted with folic acid (BER-ALG/CHS-NPs-F) for specific targeting in breast cancer. BER-ALG/CHS-NPs-F was optimized by applying the Box-Behnken design using Expert design software. Moreover, formulations are extensively evaluated in vitro for biopharmaceutical performances and tested for cell viability, cellular uptake, and antioxidant activity. The comparative pharmacokinetic study of formulation and free BER was carried out in animals for estimation of bioavailability. The particle size recorded for the diluted sample using a Malvern Zetasizer was 240 ± 5.6 nm. The ζ-potential and the predicted % entrapment efficiency versus (vs) observed were +18 mV and 83.25 ± 2.3% vs 85 ± 3.5%. The high % drug release from the NPs was recorded. The analytical studies executed using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction expressed safe combinations of the components in the formulation and physical state of the drug revealed to be amorphous in the formulation. Cytotoxicity testing demonstrated that the formulation effectively lowered the cell viability and IC50 of the tested cell line in comparison to a raw drug. The cellular uptake of BER-ALG/CHS-NPs-F was 5.5-fold higher than that of BER-suspension. The antioxidant capacities of BER-ALG/CHS-NPs-F vs BER-suspension by the DPPH assay were measured to be 62.3 ± 2.5% vs 30 ± 6%, indicating good radical scavenging power of folate-conjugated NPs. The developed formulation showed a 4.4-fold improved oral bioavailability compared to BER-suspension. The hemolytic assay intimated <2% destruction of erythrocytes by the developed formulation. The observed experimental characterization results such as cytotoxicity, cellular uptake, antioxidant activity, and improved absorption suggested the effectiveness of BER-ALG/CHS-NPs-F toward breast cancer.

Antibiotics resistance as a major public health concern: A pharmaco-epidemiological study to evaluate prevalence and antibiotics susceptibility-resistance pattern of bacterial isolates from multiple teaching hospitals.

BACKGROUND: Multi Drugs Resistance (MDR) is among the most worrisome healthcare issues resulting from inappropriate and indiscriminate utilization of antimicrobial agents which has compromised the efficacy and reliability of antimicrobial agents (AMAs). This has not only put a huge burden on the health care system but also is a major cause of morbidity and mortality. This project was designed to evaluate the prevalence of various microbial strains among patients admitted to various teaching hospitals and to assess their susceptibility and resistance towards clinically approved antibiotics. METHODS: The study was conducted during August 2021-February 2022 to determine the prevalence of common resistant strains of bacteria and to analyze their susceptibility pattern to the commonly prescribed antibiotics using standard procedures. One hundred and thirty biological samples including urine, blood, cerebrospinal fluid (CSF), wound swabs, pus and sputum were collected from the site of infection from the patients admitted at different wards of North West General Hospital (NWGH), Peshawar, Pakistan, Khyber Teaching Hospital (KTH), Peshawar Pakistan, and Hayat Abad Medical Complex (HMC) Peshawar Pakistan. Samples were collected and cultured following standard hospital procedures. The cultured samples were subjected to identification procedures including Gram staining, morphological characterization of bacterial colonies and biochemical assessments. The identified bacteria were tested for their susceptibility using Kirby-Bauer disc diffusion method. The diameter of Inhibitory Zones (DIZ) was analyzed following Clinical and Laboratory Standards Institute (CLSI) criteria. Minimum Inhibitory Concentrations (MICs) were evaluated using agar dilution method. Antimicrobials sensitivity were presented as antibiogram following CLSI M39 standard. RESULTS: A total of one hundred and thirty biological samples were collected, out of which one hundred and nine samples were positive for bacterial growth and were further processed for detailed analysis. The frequency and type of bacteria isolated from various cultures indicated that Gram negative bacteria (n = 92/109) were more dominant than Gram-positive (n = 17/109) pathogens. The most prevalent bacteria isolated was Escherichia coli (29.35 %), followed by Staphylococcus aureus (15.59 %), and Klebsiella spp, (12.84 %). In addition, other pathogens including, Enterobacter spp, Citrobacter spp, and Acinetobacter spp. showed a prevalence of 9.175 %, 8.25 %, and 5.50 % respectively. As indicated in the antbiogram, several organisms exhibited considerble decline in the sensitivies towards various antibiotics. A high percentage of resistance was observed against some antibiotics including trimethoprim, co-trimoxazole, amoxicillin/clavulanate, ciprofloxacin, piperacillin/tazobactam, cefotaxime and ceftazidime. CONCLUSION: The prevalence of resistant strains of pathogens is increasing day by day, while the antibiotics commonly prescribed against them are losing their efficacy, which is pushing the world to the era of pre-antibiotics. Unfortunately, the discovery of novel antibiotics is limited and researchers speculate that the is pushing towards pre-antibiotics era. Subsequently, efforts must be directed towards ensuring rational antibiotics use to prevent emergence of MDR pathogens. Our findings indicated that Gram negative bacteria including Escherichia coli was most prevalent. Other bacterial strains including S. aureus, Klebsiella spp, Enterobacter spp, Citrobacter spp, and Acinetobacter spp. were found among the causative agents. Unfortunately, considerable decline in the sensitivities of various bacterial isolated were observed towards the tested antibiotics. Previous studies reported the high prevalence of E. coli and S. aureus in clinical samples of Pakistani hospitals including hospitals in Peshawar and thus our findings are in agreement with the previous reports. Pharmacists being experts can play their role by promoting the optimal use of antimicrobial agents and educating healthcare professionals, patients and the public.