Therapeutic Options Research Articles

Magnetic soft microrobots for erectile dysfunction therapy

Erectile dysfunction (ED) is a major threat to male fertility and quality of life, and mesenchymal stromal cells (MSCs) are a promising therapeutic option. However, therapeutic outcomes are compromised by low MSC retention and survival rates in corpus cavernosum tissue. Here, we developed an innovative magnetic soft microrobot comprising an ultrasoft hydrogel microsphere embedded with a magnetic nanoparticle chain for MSC delivery. This design also features phenylboronic acid groups for scavenging reactive oxygen species (ROS). With a Young’s modulus of less than 1 kPa, the ultrasoft microrobot adapts its shape within narrow blood vessels, ensuring a uniform distribution of MSCs within the corpus cavernosum. Our findings showed that compared with traditional MSC injections, the MSC delivery microrobot (MSC-Rob) significantly enhanced MSC retention and survival. In both rat and beagle ED models, MSC-Rob treatment accelerated the repair of corpus cavernosum tissue and restored erectile function. Single-cell RNA sequencing (scRNA-seq) revealed that MSC-Rob treatment facilitates nerve and blood vessel regeneration in the corpus cavernosum by increasing the presence of regenerative macrophages. Overall, our MSC-Rob not only advances the clinical application of MSCs for ED therapy but also broadens the scope of microrobots for other cell therapies.

Renal remodeling by CXCL10-CXCR3 axis-recruited mesenchymal stem cells and subsequent IL4I1 secretion in lupus nephritis

AbstractHuman umbilical cord mesenchymal stem cells (hUC-MSCs) have shown potential as a therapeutic option for lupus nephritis (LN), particularly in patients refractory to conventional treatments. Despite extensive translational research on MSCs, the precise mechanisms by which MSCs migrate to the kidney and restore renal function remain incompletely understood. Here, we aim to clarify the spatiotemporal characteristics of hUC-MSC migration into LN kidneys and their interactions with host cells in microenvironment. This study elucidates that the migration of hUC-MSCs to the LN kidney is driven by elevated levels of CXCL10, predominantly produced by glomerular vascular endothelial cells through the IFN-γ/IRF1-KPNA4 pathway. Interestingly, the blockade of CXCL10-CXCR3 axis impedes the migration of hUC-MSCs to LN kidney and negatively impacts therapeutic outcomes. Single cell-RNA sequencing analysis underscores the importance of this axis in mediating the regulatory effects of hUC-MSCs on the renal immune environment. Furthermore, hUC-MSCs have been observed to induce and secrete interleukin 4 inducible gene 1 (IL4I1) in response to the microenvironment of LN kidney, thereby suppressing Th1 cells. Genetically ablating IL4I1 in hUC-MSCs abolishes their therapeutic effects and prevents the inhibition of CXCR3+ Th1 cell infiltration into LN kidneys. This study provides valuable insights into the significant involvement of CXCL10-CXCR3 axis in hUC-MSC migration to the LN kidneys and the subsequent remodeling of renal immune microenvironment. Regulating the CXCL10-CXCR3 axis and IL4I1 secretion may be developed as a novel therapeutic strategy to improve treatment outcomes of LN.

Protocol and research program of the European registry and biobank for interstitial lung diseases (eurILDreg)

Abstract Background and Aims Interstitial lung diseases (ILDs), encompassing both pediatric and adult cases, present a diverse spectrum of chronic conditions with variable prognosis. Despite limited therapeutic options beyond antifibrotic drugs and immunosuppressants, accurate diagnosis is challenging, often necessitating invasive procedures that may not be feasible for certain patients. Drawn against this background, experts across pediatric and adult ILD fields have joined forces in the RARE-ILD initiative to pioneer novel non-invasive diagnostic algorithms and biomarkers. Collaborating with the RARE-ILD consortium, the eurILDreg aims to comprehensively describe different ILDs, analyze genetically defined forms across age groups, create innovative diagnostic and therapeutic biomarkers, and employ artificial intelligence for data analysis. Methods The foundation of eurILDreg is built on a comprehensive parameter list developed and adopted by clinical experts, encompassing over 1,800 distinct parameters related to patient history, clinical examinations, diagnosis, lung function and biospecimen collection. This robust dataset is further enriched with daily assessments captured through the patientMpower app, including handheld spirometry and exercise tests, conducted on approximately 350 patients over the course of a year. This approach involves app-based daily assessments of quality of life, symptom tracking, handheld spirometry, saturation measurement, and the 1-min sit-to-stand test (1-STST). Additionally, pediatric data from the ChILD-EU registry will be integrated into the RARE-ILD Data Warehouse, with the ultimate goal of including a total of 4.000 ILD patients and over 100.000 biospecimen. Discussion The collaborative efforts within the consortium are poised to streamline research endeavors significantly, promising to advance patient-centered care, foster innovation, and shape the future landscape of interstitial lung disease research and healthcare practices. Trial Registration EurILDreg is registered in the German Clinical Trials Register (DRKS 00028968, 26.07.2022), and eurIPFreg is registered in ClinicalTrials.gov (NCT02951416).

Overestimation of clinical N-staging in microsatellite instable gastric cancers is associated with VEGF-C signaling and CD8+ T-cell dynamics

Abstract Background Microsatellite instable (MSI) gastric cancers exhibit reduced lymph node (LN) metastasis and improved survival compared to microsatellite stable (MSS) counterparts. However, to our longstanding observation, clinical N-staging (cN) is frequently overestimated in MSI cases. The clinical implications and underlying mechanisms of this discrepancy warrant further investigation. Materials and methods We conducted a comprehensive review of clinicopathological data from a 141 MSI and 1119 MSS gastric cancer patients. Expression of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 were assessed using qPCR and immunohistochemistry. High-parameter flow cytometry was employed to analyze subsets of CD8+ T cells within the tumors. Results Multivariate analysis revealed that MSI status was an independent prognostic factor, alongside the LN ratio and AJCC8 pathology staging. MSI gastric cancers exhibited a reduced LN ratio, particularly at advanced T-staging, compared to MSS counterparts, while maintaining an equivalent LN yield. Overestimation of cN by computed tomography preoperatively was frequent in MSI gastric cancers but was more commonly underestimated in MSS counterparts. VEGF-C and VEGFR-3 expression were lower in MSI tumors. MSI gastric cancers showed an increased total number of CD8+ T cells, albeit with a lower proportion of effector memory cells expressing CD45RA (EMRA) and CD8+ CXCR4+ T cells, compared to MSS counterparts. Conclusion Frequent overestimation of clinical N-staging in MSI gastric cancers is associated with VEGF-C signaling and CD8+ T-cell dynamics and should be cautiously interpreted, as it might misguide therapeutic options.

Interrelationships between affective disorders in the form of depression and obesity and overweight - A systematic review

Both depression and obesity are significant health, social and economic problems. Depressive disorders were the second most common psychiatric disorder in 2017 after anxiety disorders. According to data published by the World Health Organization (WHO), depression affects about 280 million people worldwide, which is about 3.8 percent of the population. The etiology of depressive disorders is very complex and still not fully understood. The theories described so far complement each other. The factors underlying the development of depressive disorders can be divided into biological, psychological and other factors. Eating disorders in the form of overweight and obesity result from a loss of balance between anabolic and catabolic processes. This is most often led by insufficient physical activity and excess caloric intake. Hormonal disorders, genetic factors and environmental factors may also play an important role in the pathogenesis of obesity. The steadily increasing number of people suffering from depression and obesity prompts the search for links between these two seemingly unrelated disease entities. According to current knowledge, these diseases are bi-directionally linked by genetic, psychological, metabolic and social factors. Depression is associated with an increase in the risk of obesity by about 37% relative to those without depression. Obesity is associated with an increase in the risk of depressive disorders by about 18%. Understanding the links that exist between depressive disorders and obesity enables the search for new therapeutic options. The most important conclusion from the scientific research conducted so far is the advantage of simultaneous treatment of obesity and depression over treating these disease entities individually.

Abstract A012: Aging drives TNBC lung metastasis dependency on FGFR-triggered metabolic reprogramming exposing an age-induced liability with therapeutic potential

Abstract The clinical manifestation of metastasis in a vital organ is the final stage of breast cancer progression and the main culprit of breast cancer related mortality. This remain especially problematic in the case of triple negative breast cancer (TNBC), the most aggressive type of breast cancer, often diagnosed in its metastatic form and for which chemotherapies are still the major therapeutic option. Typically, TNBC is seen as a disease of younger women, however, 20% of TNBCs occur in patients aged 65 and older, whose prognosis is equally staggering. Unfortunately, due to co-morbidities, tolerability of chemotherapies, as well as severe reduction in quality of life, majority of women above age 65 can’t or decide not to receive chemotherapy ultimately cutting their lives short. Metastatic outgrowth is largely dictated by the ability of TNBC disseminated cancer cells (DCCs) to thrive distal organs and is largely dependent on the physiology of the specific organs. However, how the aging process, a major driver of changes in organismal physiology, affects the interaction between the host organ and TNBC DCCs remains unknown. Here, we adapted several traditional syngeneic models of TNBC metastasis to old mice of different strains and coupled with RNA-seq to unveil molecular adaptations of TNBC DCCs to the aging lung. We show that the changes that occur in the lung with aging drives an increase in mitochondrial fitness in TNBC DCCs, an adaptation that is necessary for metastasis to thrive in the old lung environment. Mechanistically, our data show that the expression of FGF19, a gut hormone not normally expressed in TNBC DCCs, drives this increase in mitochondrial fitness in the old lung through an autocrine signaling axis impinging on activation of FGF-19 cognate receptor family, FGFRs. Inhibition of FGF19-FGFR signaling using an FDA- approved FGFR inhibitor not only blocks the age-induced increase in mitochondrial fitness but also effectively abolishes lung metastasis in old, but not in young, immune competent and immune compromised mice. We traced this to age-specific metastatic adaptation of TNBC lung metastasis to the increase in bile acids, the canonical regulators of FGF19 expression, in the old lung environment. Together, our work demonstrates an important contribution of age-driven metabolic reprogramming of the host to the traits that enable metastasis to thrive in the lung and provides rationale for the use of FDA-approved FGFR inhibitors for the treatment of breast cancer lung metastasis in the most vulnerable of stage IV metastatic TNBC patients, the elderly. Citation Format: Stanislav Drapela, Shiun Chang, Rojan Chimeh Rad, Vanessa Rubio, Didem Ilter, Paulo Rodriguez, Ana P. Gomes. Aging drives TNBC lung metastasis dependency on FGFR-triggered metabolic reprogramming exposing an age-induced liability with therapeutic potential [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A012.

Abstract B013: Hallmarks of progression in early neoantigen-expressing lung adenocarcinoma

Abstract Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality, largely due to its high prevalence rate and limited therapeutic options. Immunotherapy remains one of the most promising therapeutic avenues, yet further research is necessary to enhance therapy effectiveness for a broader range of patients. Central to the mechanism of immunotherapy is the detection of tumor neoantigens by cytotoxic T cells, which trigger the elimination of tumor cells. However, it is largely unknown how the early interaction between T cells and neoantigen-expressing tumor cells affects the acquisition of cancer hallmarks and tumor progression. To study this, our lab has developed the iNversion-INduced Joined neoAntigen (NINJA) genetically engineered mouse model in which we can initiate expression of a neoantigen in Kras-mutant, Trp53-null, tdTomato-expressing lung adenocarcinoma cells (KPT-NINJA). This system enables us to analyze tumor initiation, progression, and advanced LUAD development over 20 weeks in both neoantigen-expressing and non-expressing tumors. We defined cancer hallmark acquisition and tumor progression in our model by using a combination of multiplex immunofluorescence and computational algorithms to quantify tumor size, immune infiltration, metastasis, and expression of cancer molecular markers p-ERK and Ki67. We isolated tumor cell and immune cell subsets using neural networks to segment cells and tumor structures and used the colocalization of molecular markers to confirm the identity of various cell types. Our initial data validated that within immunogenic tumors there is an increase of T cell infiltration in tumors and have found immunogenic tumors are associated with overall smaller tumors at early time points. Interestingly, these tumors are associated with a decrease in p-ERK expression, suggesting immune infiltration is negatively correlated with p-ERK expression and tumor size. Together, these data indicate that increased immunogenic pressure may be disrupting early tumor proliferation and hallmark progression, shaping the trajectory of development at a very early stage. We are also correlating other molecular markers of tumor progression with immune infiltration, such as Ki67 expression, which we will colocalize with the other findings to construct a model of how tumors acquire hallmark capabilities from an immunogenic perspective. By isolating the mechanism of early tumor progression in immunogenic contexts, we can begin to predict disease trajectory. This will contribute to a better understanding of the mechanisms behind immune evasion and may uncover crucial insights to broaden immune therapy efficacy. Citation Format: Ishan Bansal, Jennifer Loza, Brian G. Hunt, Kelli Connolly, Srividhya Venkatesan, Nikhil Joshi. Hallmarks of progression in early neoantigen-expressing lung adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B013.

Dentinal tubule occlusion effects of dipotassium oxalate and diode laser combination: a single-blind in vitro study.

Dentin hypersensitivity (DH) affects many patients. Various therapeutic options have been devised to alleviate this condition by achieving dentinal tubules (DT) occlusion. This research aimed to investigate the effects of dipotassium oxalate-containing mouthwash, diode laser and their combination on DT occlusion. Forty dentin samples were obtained from 20 human single-rooted third molars, 40 dentin specimens were obtained, and exposed DT were created in vitro. They were assigned into four groups: Group 1 (n = 10), the control group where no treatment was applied; Group 2 (n = 10), a mouthwash with a 1.4% dipotassium oxalate was applied twice for 60s during a 5-day period in a shaker at 100rpm; Group 3 (n = 10), a combination of the same mouthwash and an 810nm diode laser at an output power of 0.25W in continuous mode was applied for 60s without contact at a distance of 3-4mm; and Group 4 (n = 10), only a diode laser with the same protocol was applied. Occlusion of the DT was observed by scanning electron microscopy. The analysis revealed occlusion of the DT in all treatment groups; however, the effects were more pronounced in the combined treatment group (Group 3). Compared with the test groups, the control group had significantly more open DT in 100 µm2 (p < 0.01). The difference between the Group 2 and Group 4 was not significant (p > 0.05). DT occlusion was achieved via the use of a mouthwash containing 1.4% dipotassium oxalate and an 810nm diode laser. However, the combination resulted in the greatest results and therefore may be utilized in individuals with DH.

EFFICACY OF CANNABIDIOL (CBD) IN THE TREATMENT OF ALZHEIMER'S DISEASE: A CRITICAL REVIEW OF EVIDENCE AND CLINICAL IMPLICATIONS

Introduction: This study investigates the therapeutic potential of cannabidiol (CBD) in treating Alzheimer's disease (AD), which is characterized by progressive cognitive decline, memory impairment, and behavioral changes. As traditional treatment options are limited, the exploration of alternative therapies, including CBD, has gained prominence in recent years. Objective: The aim of this research is to evaluate the efficacy of CBD in modulating neuroinflammation and oxidative stress, as well as its potential impact on slowing the progression of Alzheimer's disease. Method: A literature review was conducted using ten articles published between 2019 and 2024. Databases such as the Virtual Health Library, LILACS Plus, and Medline were utilized, applying descriptors related to CBD and Alzheimer's disease. The articles were filtered based on specific inclusion criteria, focusing on studies published in Portuguese, Spanish, and English that are freely accessible online. Results: The reviewed literature indicates that CBD may inhibit the formation of beta-amyloid plaques, a hallmark of Alzheimer's pathology, suggesting its potential for both symptom relief and slowing disease progression. Additionally, the interaction between CBD and the endocannabinoid system (ECS) highlights its role in managing cognitive decline and memory issues associated with AD. Conclusion: While the findings are promising, there is a pressing need for more rigorous clinical studies to validate the efficacy and safety of CBD in Alzheimer's treatment. This research underscores the potential of cannabinoids as a therapeutic option in managing neurodegenerative diseases.

The therapeutic efficacy of adipose mesenchymal stem cell-derived microvesicles versus infliximab in a dextran sodium sulfate induced ulcerative colitis rat model

ABSTRACT Ulcerative colitis (UC) is a chronic relapsing intestinal inflammation that is becoming of increasing incidence worldwide and has insufficient treatment. Therefore, finding effective therapies remains a priority. A dextran sodium sulfate colitis model was established to elucidate colonic layers alterations and compare adipose mesenchymal stem cell-derived microvesicles (MSC-MVs) versus infliximab (IFX) efficacy through biochemical, light, and electron microscope studies. Fifty-four rats were allocated to 4 groups: Control (Con), UC, UC+IFX, and UC+MSC-MVs groups. End body weights (BW) and serum malondialdehyde (MDA) levels were recorded. Colitis severity was estimated by disease activity index (DAI). Colonic specimens were processed to evaluate the histological structure, collagen content, surface mucous and goblet cells, CD44, TNF-α, and GFAP immune expression. Morphometric and statistical analyses were performed. The UC group revealed congested, stenosed colons, a significant decline in end BW, and a significant increase in serum MDA and DAI. Furthermore, disturbed histoarchitecture, inflammatory infiltration, depletion of surface mucous and goblet cells, increased collagen, and TNF-α expression and decreased GFAP expression were observed. Alterations were partially attenuated by IFX therapy, whereas MSC-MVs significantly improved all parameters. In conclusion, MSC-MVs were a superior therapeutic option, via attenuating oxidative stress and inflammatory infiltration, in addition to restoring intestinal epithelial integrity and mucosal barrier.

Exploring mesenchymal stem cells homing mechanisms and improvement strategies.

Mesenchymal stem cells (MSCs) are multipotent cells with high self-renewal and multilineage differentiation abilities, playing an important role in tissue healing. Recent advancements in stem cell-based technologies have offered new and promising therapeutic options in regenerative medicine. Upon tissue damage, MSCs are immediately mobilized from the bone marrow and move to the injury site via blood circulation. Notably, allogenically transplanted MSCs can also home to the damaged tissue site. Therefore, MSCs hold great therapeutic potential for curing various diseases. However, one major obstacle to this approach is attracting MSCs specifically to the injury site following systemic administration. In this review, we describe the molecular pathways governing the homing mechanism of MSCs and various strategies for improving this process, including targeted stem cell administration, target tissue modification, in vitro priming, cell surface engineering, genetic modifications, and magnetic guidance. These strategies are crucial for directing MSCs precisely to the injury site and, consequently, enhancing their migration and local tissue repair properties. Specifically, our review provides a guide to improving the therapeutic efficacy of clinical applications of MSCs through optimized in vivo administration and homing capacities.

In Situ Treatment of Refractory Perianal Fistulas in Dogs with Low-Dose Allogeneic Adipose-Derived Mesenchymal Stem Cells

Stem cell therapy in dogs has increased considerably in recent years; however, there are few publications on the treatment of perianal fistulas (PF) in this species. The aim of this open-label clinical trial was to demonstrate the efficacy and safety of a new protocol for the in situ administration of low-dose adipose-derived allogeneic stem cells (ASCs) for the treatment of refractory spontaneous perianal fistula. The methodology consisted of applying one to three doses of 5 × 106 cryopreserved allogeneic ASCs to each fistula. The study was performed in 14 dogs regardless of sex, breed, or age, with a clinical diagnosis of refractory PF. Cells diluted in phosphate-buffered saline were applied to five sites of the PF in an amount of 1 × 106 per application site. Efficacy was determined by the complete closure of the fistula, which was observed in 100% of the cases studied one month after therapy, with a subsequent follow-up of 12 to 48 months after therapy. Furthermore, safety was demonstrated by the absence of local or systemic adverse effects. In conclusion, the protocol used in this work demonstrates the efficacy without adverse effects of the in situ application of low doses of allogeneic ASCs, providing a simple, non-invasive, long-lasting and low-cost therapeutic option.

Nanomaterial-Mediated Reprogramming of Macrophages to Inhibit Refractory Muscle Fibrosis.

Orofacial muscles are particularly prone to refractory fibrosis after injury, leading to a negative effect on the patient's quality of life and limited therapeutic options. Gaining insights into innate inflammatory response-fibrogenesis homeostasis can aid in the development of new therapeutic strategies for muscle fibrosis. In this study, the crucial role of macrophages is identified in the regulation of orofacial muscle fibrogenesis after injury. Hypothesizing that orchestrating macrophage polarization and functions will be beneficial for fibrosis treatment, nanomaterials are engineered with polyethylenimine functionalization to regulate the macrophage phenotype by capturing negatively charged cell-free nucleic acids (cfNAs). This cationic nanomaterial reduces macrophage-related inflammation in vitr and demonstrates excellent efficacy in preventing orofacial muscle fibrosis in vivo. Single-cell RNA sequencing reveals that the cationic nanomaterial reduces the proportion of profibrotic Gal3+ macrophages through the cfNA-mediated TLR7/9-NF-κB signaling pathway, resulting in a shift in profibrotic fibro-adipogenic progenitors (FAPs) from the matrix-producing Fabp4+ subcluster to the matrix-degrading Igf1+ subcluster. The study highlights a strategy to target innate inflammatory response-fibrogenesis homeostasis and suggests that cationic nanomaterials can be exploited for treating refractory fibrosis.

Preventive effects of nitric oxide donors in contrast-induced nephropathy in patients undergoing coronary artery angiography: an updated systematic review and meta-analysis of 13 randomized controlled trials.

Contrast-induced nephropathy (CIN) is associated with increased mortality and morbidity in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention (PCI). We aimed to assess the latest evidence on the preventive effects of nitric oxide (NO) donors in CIN patients undergoing CAG/PCI. We conducted a comprehensive systematic review and meta-analysis of RCTs from PubMed, Web of Science, Scopus, Embase, and Cochrane searches until May 5th, 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using (R version 4.3). Our analysis included 13 RCTs encompassing 3,550 patients. NO donors were significantly associated with a decreased incidence of CIN compared to placebo either as an oral administration (RR: 0.33 with 95% CI [0.26, 0.42], P < 0.01) or IV infusions (RR: 0.56 with 95% CI [0.40, 0.78], P < 0.01). Moreover, NO donors were significantly associated with decreased serum creatinine levels compared to placebo either as an oral administration (MD: - 0.07 with 95% CI [- 0.10, - 0.04], P < 0.01) or IV infusions (MD: - 0.07 with 95% CI [- 0.09, - 0.04], P < 0.01). In terms of safety, NO donors were significantly associated with a decreased incidence of major adverse cardiac events (MACE) compared to placebo as an oral administration (RR: 0.64 with 95% CI [0.45, 0.89], P < 0.01). However, there was no significant difference between NO donors as IV infusions and placebo in MACE (RR: 0.68 with 95% CI [0.38, 1.21], P = 0.18). Finally, NO donors were significantly associated with a decreased incidence of all-cause mortality compared to placebo as an oral administration (RR: 0.58 with 95% CI [0.36, 0.94], P = 0.03). Nevertheless, there was no statistically significant difference in all-cause mortality between IV infusions of NO donors and placebo (RR: 1.84 with 95% CI [0.40, 8.52], P = 0.44). NO donors as adjunct therapy are associated with reduced incidence of CIN and decreased serum creatinine levels, either as an oral or IV administration. They were also associated with reduced incidence of MACE, all-cause mortality, and recurrent myocardial infarction as an oral administration, which makes this simple, low-cost intervention an important therapeutic option in patients undergoing CAG/PCI.

From past to present, exploring the applications of mupirocin ointment: A comprehensive review

Mupirocin (MUP), a potent antibacterial agent, has been a cornerstone of topical antimicrobial therapy for several decades. As an older, yet widely used antibiotic, MUP has exhibited efficacy against various bacterial strains, making it a versatile tool in the management of a range of infections. The review synthesizes available literature to highlight the evolution of MUP, from its initial discovery to its current status as a go-to topical antibiotic. In the era of rising antibiotic resistance, MUP is positioned as a valuable therapeutic option due to its broad-spectrum activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Emphasis is placed on its distinctive role in different infections, enhanced efficacy with different additives, and newer drug delivery strategies.In addition to its classical applications in impetigo and other superficial skin infections, this review delves into emerging indications and novel uses of MUP, potentially expanding its clinical utility. The exploration of combination therapies, alternative formulations, and ongoing research endeavors will contribute to a forward-looking perspective on the role of MUP in future antimicrobial strategies.

Non-coding RNAs modulation in breast cancer radioresponse: mechanisms and therapeutic implications.

Breast cancer is the most frequent type of cancer in women, with significant incidence and fatality rates. Radiation therapy is an important therapeutic option for breast cancer patients. However, tumor cells' resistance to radiation can limit therapy efficacy, resulting in recurrence and death. Non-coding RNAs (ncRNAs) are aclass of small RNA molecules that do not translate into proteins but can affect the translation of target mRNA. Several investigations on breast cancer have demonstrated abnormal expression of ncRNAs in response to radiation. Non-coding RNAs are essential in controlling numerous processes such as DNA damage response, cancer stem cell pathways, cell cycle regulation, cell death, and inflammation. Dysregulation of ncRNAs after irradiation influences radiosensitivity or radioresistance of breast cancer cells. Understanding the molecular mechanisms underlying Radiation response can lead to innovative treatment ways to reduce breast cancer radioresistance and increase radiotherapy's efficacy. This review summarizes current research on ncRNA dysregulation following irradiation and analyzes ncRNAs' function and mechanism in modifying breast cancer cell radiosensitivity and radioresistance.

Different regimens for eradication of Helicobacter pylori infection in children: a randomized controlled trial.

As an empirical treatment for children with H. pylori infection, CTT is safe and provides the highest eradication rate. HT, ST, and CT might not be superior to TT. This study was registered at the Pan African Clinical Trials Registry, Cochrane South Africa, under the identifier PACTR202201686010590. Date of registration: 04 January 2022. • Triple therapy has been the standard eradication regimen for pediatric H. pylori infection. The efficacy of triple therapy has decreased in many countries due to increased antibiotic resistance. • This randomized controlled trial is the first to compare triple therapy, sequential therapy, hybrid therapy, concomitant therapy, and ciprofloxacin-based triple therapy for the eradication of pediatric H. pylori infection. Triple therapy exhibited the lowest eradication rate among the studied regimens, suggesting it may not be an adequate therapeutic option for infected children. Ciprofloxacin-based triple therapy appears to be a safe and effective therapeutic choice for pediatric H. pylori infection. Additionally, this study provides the first reported eradication rate of hybrid therapy in pediatric H. pylori infection.

Nuclear PD-L1 compartmentalization suppresses tumorigenesis and overcomes immunocheckpoint therapy resistance in mice via histone macroH2A1.

Canonically PD-L1 functions as the inhibitory immune checkpoint on cell surface. Recent studies have observed PD-L1 expression in the nucleus of cancer cells. But the biological function of nuclear PD-L1 (nPD-L1) in tumor growth and antitumor immunity is unclear. Here we enforced nPD-L1 expression and established stable cells. nPD-L1 suppressed tumorigenesis and aggressiveness in vitro and in vivo. Compared with PD-L1 deletion, nPD-L1 expression repressed tumor growth and improved survival more markedly in immunocompetent mice. Phosphorylated AMPKα (p-AMPKα) facilitated nuclear PD-L1 compartmentalization and then cooperated with it to directly phosphorylate S146 of histone variant macroH2A1 (mH2A1) to epigenetically activate expression of genes of cellular senescence, JAK/STAT, and Hippo signaling pathways. Lipoic acid (LA) that induced nuclear PD-L1 translocation suppressed tumorigenesis and boosted antitumor immunity. Importantly, LA treatment synergized with PD-1 antibody and overcame immune checkpoint blockade (ICB) resistance, which likely resulted from nPD-L1-increased MHC-I expression and sensitivity of tumor cells to interferon-γ. These findings offer a conceptual advance for PD-L1 function and suggest LA as a promising therapeutic option for overcoming ICB resistance.

IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma.

Chondrosarcomas, a rare form of bone sarcomas with multiple subtypes, pose a pressing clinical challenge for patients with advanced or metastatic disease. The lack of US Food and Drug Administration (FDA)-approved medications underscores the urgent need for further research and development in this area. Patients and their families face challenges as there are no systemic therapeutic options available with substantial effectiveness. A significant number (50-80%) of chondrosarcomas have a mutation in the isocitrate dehydrogenase (IDH) genes. This review focuses on IDH-mediated pathogenesis and recent pharmacological advances with novel IDH inhibitors, explores their potential therapeutic value, and proposes potential future avenues for clinical trials combining IDH inhibitors with other systemic agents for chondrosarcomas.

Effects of Autologous Platelet Concentrate Injection on Persistent Macular Hole

Purpose: To evaluate the effects of secondary pars plana vitrectomy (PPV) with autologous platelet concentrate (APC) injection in patients with a persistent macular hole that failed to close after the primary surgery.Methods: This study included 10 eyes of 10 patients who required secondary PPV and APC injection due to unsuccessful hole closure following primary macular hole surgery between February 2021 and July 2023. We measured the minimum and base diameters of the holes before primary and secondary PPV, respectively. Furthermore, we evaluated the anatomical closure of the holes and changes in best corrected visual acuity (BCVA) for 6 months following secondary PPV.Results: The mean age of the 10 patients was 61.6 ± 9.5 years. Prior to the primary PPV, the mean BCVA (LogMAR) was 1.6 ± 0.7, the mean minimum diameter of the hole was 654.4 ± 98.9 μm, and the mean base diameter of the hole was 1,135.4 ± 276.5 μm. Prior to the secondary PPV with APC injection, the mean BCVA (LogMAR) was 1.3 ± 0.7, the mean minimum diameter of the hole was 666.8 ± 270.2 μm and the mean base diameter of the hole was 845.4 ± 292.4 μm. Following secondary surgery, all holes were successfully closed, the mean BCVA (LogMAR) was 0.9 ± 0.6 and the BCVA was significantly improved (&lt;i&gt;p&lt;/i&gt; = 0.007).Conclusions: PPV with APC injection can be an effective therapeutic option for persistent macular hole that failed to close following primary surgery both in terms of anatomical and functional outcomes.