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Antibiotics are successful in promoting health quality by preventing various infectious diseases and minimizing mortality and morbidity all over the world. However, the indiscriminate use of antibiotics has led to the emergence of multi-drug-resistant bacteria, which pose a serious threat to health care sector. Therefore, it is necessary to develop novel antimicrobial agents with versatile characteristics, such as antibacterial activity, low toxicity, wound healing potency, and antioxidant property. In this context, silver chitosan nanoparticles were synthesized in the present study, and their physical characterization revealed that the size of synthesized chitosan–silver nanoparticles was 14–25 nm, with positive surface charge. The functional groups and crystalline nature of the nanoparticles were confirmed by FT-IR and XRD analysis. Further, the silver chitosan nanoparticles showed antibacterial activity against two important clinical pathogens, S. aureus and E. coli. The MTT assay carried out in the present study showed that the synthesized nanoparticles are non-toxic to host cells. A scratch assay on fibroblast cells (L292) demonstrated that the silver chitosan nanoparticles showed promising wound healing activity. A fluorescent DCFH-DA staining assay revealed anantioxidant property of the synthesized nanoparticles. Overall, the study emphasizes the versatile nature of synthesized chitosan–silver nanoparticles, suggesting their great compatibility for biomedical applications. [ABSTRACT FROM AUTHOR]

Creatine transporter (CrT1) mediates cellular uptake of creatine (Cr), a nutrient pivotal in maintaining energy homeostasis in various tissues including intestinal epithelial cells (IECs). The impact of CrT1 deficiency on the pathogenesis of various psychiatric and neurological disorders has been extensively investigated. However, there are no studies on its regulation in IECs in health and disease. Current studies have determined differential expression of CrT1 along the length of the mammalian intestine and its dysregulation in inflammatory bowel disease (IBD)-associated inflammation and Adherent Invasive E. coli (AIEC) infection. CrT1 mRNA and protein levels in normal intestines and their alterations in inflammation and following AIEC infection were determined in vitro in model IECs (Caco-2/IEC-6) and in vivo in SAMP1/YitFc mice, a model of spontaneous ileitis resembling human IBD. CrT1 is differentially expressed in different regions of mammalian intestines with its highest expression in jejunum. In vitro, CrT1 function (Na+-dependent 14C-Cr uptake), expression and promoter activity significantly decreased following TNFα/IL1β treatments and AIEC infection. SAMP1 mice and ileal organoids generated from SAMP1 mice also showed decreased CrT1 mRNA and protein compared to AKR controls. Our studies suggest that Cr deficiency in IECs secondary to CrT1 dysregulation could be a key factor contributing to IBD pathogenesis. [ABSTRACT FROM AUTHOR]

Previously we have reported the isoliensinine (ISO) potentates the therapeutic potential of cisplatin in cisplatin resistant colorectal cancer stem cells. The present study evaluates the chemo‐sensitizing potential of the combinatorial regimen of ISO and Paclitaxcel (PTX) on multidrug‐resistant (MDR)‐HCT‐15 cells to reduce the dose requirement of both ISO and PTX. The results of the present study suggest that treatment with the combinatorial regimen of ISO and PTX enhanced the cytotoxic effect with resultant increase in apoptosis in MDR‐HCT‐15 cells as evident from the altered cellular morphology, G2/M cell cycle arrest, propidium iodide uptake, Annexin V, increased intracellular Ca2+ accumulation, decreased mitochondrial membrane potential, diminished ATP production, PARP‐1 cleavage, altered expression of ERK1/2, and apoptotic proteins. Treatment with combinatorial regimen of ISO and PTX also modulated the expression of the transcription factors SOX2, OCT4 which determine the stemness of cancer cells. Thus, results of the present study suggest that ISO and PTX combination regimen induces apoptosis in MDR‐HCT‐15 in a synergistic manner. [ABSTRACT FROM AUTHOR]

Several research reports delineated the significant role of miRNAs in cancer proliferation, and their modulatory role in cancer mitigation, and drug resistance. Melanoma cells have been acquiring stemness to several chemotherapeutic agents through drug efflux proteins, epigenetic modulation, and DNA repair. miRNAs could be applied as novel therapeutic modalities for treating several kinds of cancers to modulate these mechanisms involved in stemness. Nanocarriers to carry these tumor-targeting miRNAs to modulate stemness are a prominent strategy to overcome their low penetrability, minimal stability, and nonspecificity. We have searched several public databases such as PubMed, Medline, Google scholar, and NLM and obtained the information pertinent to the miRNA-based nanocarrier systems to target stemness through epigenetic modulation in melanomas. This review delineates that various miRNAs can modulate the stemness in melanomas by specific intricate epigenetic signaling, and other cell-based signaling mechanisms. Specific nanocarrier formulations with specific miRNAs are optimal methods to deliver these miRNAs in order to achieve significant entrapment efficiency, loading efficiency, and stability. Furthermore, the combinatorial regimen of FDA-approved chemotherapeutic molecules with tumor-targeting miRNAs and chemotherapy combined with nanocarriers can efficiently deliver the utmost therapeutic window by targeting tumor matrix, invasion, metastasis, and angiogenesis in melanomas. Substantial research should focus on the clinical application of this gene therapy in melanomas using these low immunogenic, highly degradable, and biocompatible combinatorial nanotherapeutic regimens. [ABSTRACT FROM AUTHOR]

Cisplatin chemotherapy to the colorectal cancer cells (CRCs) is accompanied by dose‐limiting adverse effects along with the acquisition of drug resistance implicating low therapeutic outcomes. The present study is aimed to evaluate the chemosensitizing efficacy of neferine/isoliensinine or combinatorial regimen of neferine/isoliensinine with cisplatin against CSCs (cisplatin resistant colon stem cells). CSCs were developed using pulse exposure of cisplatin to parental HCT‐15 cells. Neferine/isoliensinine or combinatorial regimens of Neferine/isoliensinine and cisplatin exhibited a stronger cytotoxic activity against CSCs compared to control. IC50 doses were found to be 6.5 μM for neferine, 12.5 μM for isoliensinine, and 120 μM for cisplatin respectively. Furthermore, the combinatorial regimen of a low dose of cisplatin (40 μM) with 4 μM neferine/8 μM isoliensinine induced cell death in a synergistic manner as described by isobologram. Neferine/isoliensinine could confer extensive intracellular reactive oxygen species generation in CSCs. Neferine/isoliensinine or combinatorial regimens dissipated mitochondrial membrane potential and enhanced intracellular [Ca2+]i, which were measured by spectroflurimetry. Furthermore, these combinatorial regimens induced a significant increase in the sub G0 phase of cell cycle arrest and PI uptake and alleviated the expression of ERCC1 in CSCs. Combinatorial regimens or neferine/isoliensinine treatments downregulated the cell survival protein expression (PI3K/pAkt/mTOR) and activated mitochondria‐mediated apoptosis by upregulating Bax, cytochrome c, caspase‐3, and PARP cleavage expression while downregulating the BCl‐2 expression in CSCs. Our study confirms the chemosensitizing efficacy of neferine/isoliensinine or combinatorial regimens of neferine/isoliensinine with a low dose of cisplatin against CSCs. [ABSTRACT FROM AUTHOR]

Background: The incidence and mortality of gynaecological cancers can significantly impact women's quality of life and increase the health care burden for organisations globally. The objective of this study was to evaluate global inequalities in the incidence and mortality of gynaecological cancers in 2022, based on The Global Cancer Observatory (GLOBOCAN) 2022 estimates. The future burden of gynaecological cancers (GCs) in 2050 was also projected., Methods: Data regarding to the total cases and deaths related to gynaecological cancer, as well as cases and deaths pertaining to different subtypes of GCs, gathered from the GLOBOCAN database for the year 2022. Predictions for the number of cases and deaths in the year 2050 were derived from global demographic projections, categorised by world region and Human Development Index (HDI)., Results: In 2022, there were 1 473 427 new cases of GCs and 680 372 deaths. The incidence of gynecological cancer reached 30.3 per 100 000, and the mortality rate hit 13.2 per 100 000. The age-standardised incidence of GCs in Eastern Africa is higher than 50 per 100 000, whereas the age-standardised incidence in Northern Africa is 17.1 per 100 000. The highest mortality rates were found in East Africa (ASMR (age-standardised mortality rates) of 35.3 per 100 000) and the lowest in Australia and New Zealand (ASMR of 8.1 per 100 000). These are related to the endemic areas of HIV and HPV. Very High HDI countries had the highest incidence of GCs, with ASIR (age-standardised incidence rates) of 34.8 per 100 000, and low HDI countries had the second highest incidence rate, with an ASIR of 33.0 per 100 000. Eswatini had the highest incidence and mortality (105.4 per 100 000; 71.1 per 100 000) and Yemen the lowest (5.8 per 100 000; 4.4 per 100 000). If the current trends in morbidity and mortality are maintained, number of new cases and deaths from female reproductive tract tumours is projected to increase over the next two decades., Conclusions: In 2022, gynaecological cancers accounted for 1 473 427 new cases and 680 372 deaths globally, with significant regional disparities in incidence and mortality rates. The highest rates were observed in Eastern Africa and countries with very high and low HDI, with Eswatini recording the most severe statistics. If current trends continue, the number of new cases and deaths from gynaecological cancers is expected to rise over the next two decades, highlighting the urgent need for effective interventions., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Previous studies described that asthma patients who received corticosteroid therapy have been constrained by the corticosteroid resistance subsequently fostered to severe refractory asthma. In this review, we discussed the implications of TSLP, RXR, the role of STAT5-activating cytokines, and IL-33/NH-cell signaling pathways, and recent clinical evidence on TSLP blockers in steroid-resistant asthma. We have searched several public databases such as Pubmed, Scopus, and Relemed and obtained information pertinent to the TSLP, RXR, TSLP blockers, the STAT5-activating cytokines, and IL-33. We discussed the multiple cell signaling mechanisms underlying steroid resistance. Blocking the TSLP and other key signaling molecules like STAT5 can retrieve the sensitivity of natural helper-cells to corticosteroids. RXR derivatives treatment can modulate the activity of TSLP, which further modulates steroid resistance in severe asthmatic patients and in patients with refractory asthma. We discussed the steroid-resistance mediated by the Th2 cells and Th2-driven eosinophilia upon corticosteroid intake. Thus, this review will be beneficial for clinicians and molecular biologists to explore the inflammatory pathways associated with refractory asthma conditions and develop novel therapies against corticosteroid-resistant asthma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Magnetic calcium phosphate nanoparticles are biocompatible and have attracted much attention as biomaterials for bone tissue engineering and theranostic applications. In this study, we report the fabrication of a biocompatible magnetic nickel ferrite supported fluorapatite nanoparticle as a bone substitute material with hyperthermia potential using a facile wet precipitation approach. The composition and magnetic properties of the sample were analyzed using X-ray diffraction (XRD) and a vibrating sample magnetometer (VSM). The presence of both magnetic (NiFe 2 O 4 and γ-Fe 2 O 3 ) and fluorapatite phases was identified, and the sample exhibited ferromagnetic behavior with saturation magnetization and coercivity of 3.08 emu/g and 109 Oe, respectively. The fabricated sample achieved the hyperthermia temperature of ∼43 °C under tumor mimic conditions (neglecting Brownian relaxation) in 2.67 min, and the specific loss power (SLP) was estimated to be 898 W/g (Ni+Fe) which is sufficient to prompt irreversible cell apoptosis. Biocompatibility of the synthesized nanoparticle was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay with fibroblast NIH 3T3 and L929 cells. An in vitro drug release experiment was conducted at pH 5 (tumor mimic) and 7.4 (physiological), which revealed a release of 49.8% in the former and 11.6% in the latter pH for 11 days. The prepared sample showed antibacterial activity against S. aureus .