Synergistic berberine chloride and Curcumin-Loaded nanofiber therapies against Methicillin-Resistant Staphylococcus aureus Infection: Augmented immune and inflammatory responses in zebrafish wound healing.

BACKGROUND: Wound healing pivots on a finely orchestrated inflammatory cascade, critical for tissue repair. Chronic wounds, compounded by persistent inflammation and susceptibility to infection, pose formidable clinical challenges. Nanofiber dressings offer promising avenues for wound care, yet their interaction with inflammation and infection remains elusive. We aim to delineate the inflammatory cascade preceding wound closure and assess Cu@Bbc nanofibers' therapeutic efficacy in mitigating inflammation and combating infection. Their unique attributes suggest promise in modulating inflammation, fostering tissue regeneration, and preventing microbial colonization. Investigating the intricate interplay between nanofiber scaffolds, inflammation, and infection may unveil mechanisms of enhanced wound healing. Our findings could stimulate the development of tailored dressings, urgently needed for effective wound management amidst immune dysregulation, infection, and inflammation. METHODS: In this investigation, we synthesized Cu@Bbc nanofibers, incorporating curcumin and berberine chloride, for wound healing applications. We evaluated their individual and combined antibacterial, anti-biofilm, and antioxidant activities, alongside binding affinity with pro-inflammatory cytokines through molecular docking. Morphological characterization was conducted via SEM, FTIR assessed functional groups, and wettability contact angle measured hydrophobic properties. The physical properties, including tensile strength, swelling behavior, and thermal stability, were evaluated using tensile testing, saline immersion method and thermogravimetric analysis. Biodegradability of the nanofibers was assessed through a soil burial test. Biocompatibility was determined via MTT assay, while wound healing efficacy was assessed with in vitro scratch assays. Controlled drug release and antibacterial activity against MRSA were examined, with in vivo assessment in a zebrafish model elucidating inflammatory responses and tissue remodeling. RESULTS: In this study, the synergistic action of curcumin and berberine chloride exhibited potent antibacterial efficacy against MRSA, with significant anti-mature biofilm disruption. Additionally, the combination demonstrated heightened antioxidant potential. Molecular docking studies revealed strong binding affinity with pro-inflammatory cytokines, suggesting a role in expediting the inflammatory response crucial for wound healing. Morphological analysis confirmed nanofiber quality, with drug presence verified via FTIR spectroscopy. Cu@Bbc demonstrated higher tensile strength, optimal swelling behavior, and robust thermal stability as evaluated through tensile testing and thermogravimetric analysis. Additionally, the Cu@Bbc nanofiber showed enhanced biodegradability, as confirmed by the soil burial test. Biocompatibility assessments showed favorable compatibility, while in vitro studies demonstrated potent antibacterial activity. In vivo zebrafish experiments revealed accelerated wound closure, re-epithelialization, and heightened immune response, indicative of enhanced wound healing. CONCLUSION: In summary, our investigation highlights the efficacy of Cu@Bbc nanofibers, laden with curcumin and berberine chloride, in displaying robust antibacterial and antioxidant attributes while also modulating immune responses and inflammatory cascades essential for wound healing. These results signify their potential as multifaceted wound dressings for clinical implementation.

Dark fermentative hydrogen production: Potential of food waste as future energy needs.

Globally, food waste (FW) is found to be one of the major constituents creating several hurdles in waste management. On the other hand, the energy crisis is increasing and the limited fossil fuel resources available are not sufficient for energy needed for emerging population. In this context, biohydrogen production approach through valorization of FW is emerging as one of the sustainable and eco-friendly options. The present review explores FW sources, characteristics, and dark fermentative production of hydrogen along with its efficiency. FW are highly biodegradable and rich in carbohydrates which can be efficiently utilized by anaerobic bacteria. Based on the composition of FW, several pretreatment methods can be adapted to improve the bioavailability of the organics. By-products of dark fermentation are organic acids that can be integrated with several secondary bioprocesses. The versatility of secondary products is ranging from energy generation to biochemicals production. Integrated approaches facilitate in enhanced energy harvesting along with extended wastewater treatment. The review also discusses various parameters like pH, temperature, hydraulic retention time and nutrient supplementation to enhance the process efficiency of biohydrogen production. The application of solid-state fermentation (SSF) in dark fermentation improves the process efficiency. Dark fermentation as the key process for valorization and additional energy generating process can make FW the most suitable substrate for circular economy and waste based biorefinery.

Applications of Neural Network-Based Plan-Cancer Method for Primary Diagnosis of Mesothelioma Cancer.

"Malignant mesothelioma (MM)" is an uncommon although fatal form of cancer. The proper MM diagnosis is crucial for efficient therapy and has significant medicolegal implications. Asbestos is a carcinogenic material that poses a health risk to humans. One of the most severe types of cancer induced by asbestos is "malignant mesothelioma." Prolonged shortness of breath and continuous pain are the most typical symptoms of the condition. The importance of early treatment and diagnosis cannot be overstated. The combination "epithelial/mesenchymal appearance of MM," however, makes a definite diagnosis difficult. This study is aimed at developing a deep learning system for medical diagnosis MM automatically. Otherwise, the sickness might cause patients to succumb to death in a short amount of time. Various forms of artificial intelligence algorithms for successful "Malignant Mesothelioma illness" identification are explored in this research. In relation to the concept of traditional machine learning, the techniques support "Vector Machine, Neural Network, and Decision Tree" are chosen. SPSS has been used to analyze the result regarding the applications of Neural Network helps to diagnose MM.

A Systematic Review on Prevalence and Assessment of Sexual Dysfunction in Vitiligo.

OBJECTIVE: Vitiligo is a common depigmenting disorder with significant psychosocial consequences. Vitiligo has been associated with psychological disorders such as depression, low self-esteem, anxiety, and sexual dysfunction (SD). In recent years, there is an increase in the number of studies looking into the impact of vitiligo on sexual functions. This systematic review investigates the assessment and prevalence of SD in vitiligo patients. MATERIALS AND METHODS: We carried out a systematic search for observational studies on the prevalence of SD in vitiligo patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines were used to prepare this systematic review. We searched PubMed, Scopus, Google Scholar, and the Cochrane Library databases. RESULTS: We observed 308 studies for screening. Finally, 12 studies that meet the eligibility criteria were included in this study. The prevalence of SD ranged from 2.7 to 82.0%. Most of the studies used the dermatology life quality index (DLQI) to assess SD. Our findings also show that vitiligo patients were more probably experience symptoms of depression and anxiety, one of the risk factors for SD. CONCLUSION: Psychological comorbidities are related to a high risk of SD in vitiligo patients. Further prospective longitudinal studies are required to investigate the causal factors for SD in vitiligo patients.

Facile synthesis, physiochemical characterization and bio evaluation of sulfadimidine capped cobalt nanoparticles.

Due to their less expensive, environment friendly nature, and their natural abundance of cobalt have attained more significant attention for the synthesis of cobalt nanoparticles. In the present study, we report the facile synthesis of cobalt nanoparticles using a straight forward chemical reduction approach of cobalt chloride with sodium borohydride and capping of sulfadimidine. sulfadimidine has strong capping eligibility on the surface of nanoparticles due to its chemical stability and is an applicable as stabilizer due to the existence of an amine bond. The as-synthesized sulfadimidine stabilized cobalt nanoparticles (Co-SD NPs) were characterized by using various spectroscopic and microscopic analysis like UV-Visible spectroscopy (UV-Vis), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), High-Resolution Transmission electron microscopy (HR-TEM), and Fourier-transform infrared spectroscopy (FT-IR). The XRD analysis exhibited the triclinic crystal structure of the as-synthesized cobalt nanoparticles and FT-IR analysis confirmed the capping of sulfadimidine via monodentate interaction. The HR-TEM analysis displayed the size of the cobalt nanoparticles approximately 3-5 nm. The antibacterial properties of the sulfadimidine stabilized cobalt nanoparticles (Co-SD NPs) were tested against various bacterial strains such as Klebsiella pneumonia (KP), Escherichia coli (EC) and Pseudomonas syringae (PS) by using agar disc diffusion approach. The results of sulfadimidine capped cobalt nanoparticles displayed the enhanced biological properties against the tested gram-negative bacteria.

In vitro antimicrobial activity and comparison of the herbal extracts and sodium hypochlorite against primary plaque colonizers.

NaClO is not suitable as a root canal irrigant because of its cytotoxicity. Good biocompatibility irrigants are required to have antibacterial activity. Many herbal products like Bee glue, Noni juice and Azadirachta indica have such properties. This study aims to investigate the possible effects of propolis, MCJ and Neem on bacterial infections and cytotoxicity in primary plaque colonizers. Direct contact and agar diffusion tests evaluated the antibacterial activity of herbal products against Fusobacterium, Candida albicans and Prevotella. The CCK 8 test determined the influence of these herbal products on the proliferation of human apical papilla stem cells (hSCAPs) and human periodontal fibroblasts (hPDLFs). A migration assay test was performed in addition to quantitative real-time PCR which measured osteogenic differentiation in hSCAPs. All herbal extracts tested in this study exhibited antibacterial activity comparable to NaClO against bacterial infections, while the strongest bacteriostatic effect was shown in the herbal treated group. These extracts had much weaker effects on the proliferation and migration of hSCAPs and hPDLFs as calculated by the CCK-8 assay against NaClO. Bee glue treatment had the most potent effect on osteogenic differentiation, followed by treatment with Noni juice and Azadirachta indica (Neem), while NaClO showed the lowest effect. For primary plaque colonizers of immature or advanced permanent teeth, Bee glue, Noni juice, and Azadirachta indica can be promising irrigants with good biocompatibility. Direct contact process and agar diffusion studies have tested the antibacterial activity against Fusobacterium, Candida albicans and Prevotella. The CCK 8 test determined the influence of these three plants on the proliferation of human apical papilla stem cells (hSCAPs) and human periodontal fibroblasts (hPDLFs). In order to examine migration ability, migration assay test was performed. Alizarin red staining, alkaline phosphatase (ALP) staining and quantitative real-time PCR measured osteo-/odontogenic differentiation in hSCAPs. All herbal extracts tested in this study exhibited antibacterial activity comparable to NaClO against bacterial infections, while the strongest bacteriostatic effect was shown in the treated group. These extracts had much weaker effects on the proliferation and migration of hSCAPs and hPDLFs as calculated by the CCK-8 assay against NaClO. Bee glue treatment had the most potent effect on osteo-odontogenic differentiation, followed by treatment with Noni juice and Azadirachta indica (Neem), while NaClO showed the lowest effect. For primary plaque colonizers of immature or advanced permanent teeth, Bee glue, Noni juice and Azadirachta indica (Neem) can be promising irrigants.

Design and synthesis of tetrahydropyridothieno[2,3-d]pyrimidine scaffold based epidermal growth factor receptor (EGFR) kinase inhibitors: the role of side chain chirality and Michael acceptor group for maximal potency.

HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.

Chair to boat interconversion and face to face interactions in isomeric aryl-substituted perhydrocyclopentaquinolizines.

The structure and the conformation of the two isomeric 3,5-di(4-methoxyphenyl)perhydrocyclopenta[ij]quinolizines 1 and 2 have been determined by a combination of NOE experiments, analysis of vicinal J coupling constants, and DFT computations. The two aryl rings were found to exhibit a face to face disposition, and variable-temperature NMR spectra allowed the determination of the corresponding rotation barriers, as well as chair to boat and nitrogen inversion processes of the quinolizine rings. The structure and the conformation of the two corresponding ammonium salts 1-H+ and 2-H+ were also obtained in solution by the same techniques: in addition, their solid-state structures were determined by X-ray diffraction.