Efficacy and Safety of Stem Cell Therapy for Orthopedic Conditions, Including Osteoarthritis and Bone Defects.

INTRODUCTION: Orthopedic conditions like osteoarthritis and bone defects pose significant challenges due to their impact on individuals' quality of life. Traditional treatments often provide only symptomatic relief, necessitating alternative therapies for long-term management. Stem cell therapy has grabbed attention for its regenerative and immunomodulatory properties, offering potential for tissue repair and functional restoration. OBJECTIVE: This study aims to assess the efficacy and safety of stem cell therapy for orthopedic conditions, specifically osteoarthritis and bone defects. MATERIALS AND METHODS: A retrospective cross-sectional study analyzed data from patients who underwent stem cell therapy for osteoarthritis or bone defects between January and September 2023. Outcome measures focused on pain and function improvements using tools such as Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), alongside radiographic assessments. Adverse events, range of motion, quality of life, and demographic factors were also examined. Data were collected from electronic medical records while maintaining patient confidentiality. Descriptive statistics using SPSS (IBM Corp., Armonk, NY, USA) were employed to analyze patient characteristics, treatment variables, and outcomes, with statistical significance determined using Chi-square test and Independent t-test. RESULTS: Out of 50 individuals, the majority, i.e., 35 (or 70%), were diagnosed with osteoarthritis, while the remaining 15 (30%) had bone defects. Treatment outcomes showed significant improvements in pain and function, with a decrease in mean VAS and WOMAC scores at the six-month follow-up. Seven participants (28%) reported adverse events, and two participants (8%) experienced serious adverse events. CONCLUSION: Stem cell therapy shows promise for treating orthopedic conditions like osteoarthritis and bone defects. While demonstrating efficacy in pain management and functional improvement, safety considerations warrant further investigation and optimization of treatment protocols. Future research should focus on refining stem cell therapy techniques and addressing safety concerns to maximize its therapeutic potential in orthopedic practice.

miR-122-5p Promotes Cowshed Particulate Matter2.5-Induced Apoptosis in NR8383 by Targeting COL4A1.

It is well known that Particulate Matter2.5 (PM2.5) has a major adverse effect on the organism. However, the health hazards of livestock farm PM2.5 to humans and animals are not yet known, and the role of miRNAs in the cellular damage induced by livestock farm PM2.5 is also unclear. Therefore, our study used cowshed PM2.5 to stimulate rat alveolar macrophage NR8383 to construct an in vitro injury model to investigate the effect of miR-122-5p on PM2.5-induced apoptosis in the NR8383. The level of apoptosis was quantified by flow cytometry and Hoechst 33342/PI double staining. Furthermore, the potential target gene Collagen type IV alpha (COL4A1) of miR-122-5p was identified through the use of bioinformatics methods. The results demonstrated a decline in cell viability and an increase in apoptosis with rising PM2.5 concentrations and exposure durations. The transfection of miR-122-5p mimics resulted in an upregulation of the pro-apoptotic protein Bcl-xL/Bcl-2 and activation of cleaved caspase-3 while inhibiting the anti-apoptotic protein B-cell lymphoma-2. The experimental data indicate that miR-122-5p is involved in the apoptotic process by targeting COL4A1. Furthermore, the overexpression of COL4A1 was observed to enhance the PM2.5-activated PI3K/AKT/NF-κB signaling pathway, which contributed to the inhibition of apoptosis. This finding offers a promising avenue for the development of therapeutic strategies aimed at mitigating cellular damage induced by PM2.5 exposure.

Poly (I:C)-Induced microRNA-30b-5p Negatively Regulates the JAK/STAT Signaling Pathway to Mediate the Antiviral Immune Response in Silver Carp (Hypophthalmichthys molitrix) via Targeting CRFB5.

In aquaculture, viral diseases pose a significant threat and can lead to substantial economic losses. The primary defense against viral invasion is the innate immune system, with interferons (IFNs) playing a crucial role in mediating the immune response. With advancements in molecular biology, the role of non-coding RNA (ncRNA), particularly microRNAs (miRNAs), in gene expression has gained increasing attention. While the function of miRNAs in regulating the host immune response has been extensively studied, research on their immunomodulatory effects in teleost fish, including silver carp (Hyphthalmichthys molitrix), is limited. Therefore, this research aimed to investigate the immunomodulatory role of microRNA-30b-5p (miR-30b-5p) in the antiviral immune response of silver carp (Hypophthalmichthys molitrix) by targeting cytokine receptor family B5 (CRFB5) via the JAK/STAT signaling pathway. In this study, silver carp were stimulated with polyinosinic-polycytidylic acid (poly (I:C)), resulting in the identification of an up-regulated miRNA (miR-30b-5p). Through a dual luciferase assay, it was demonstrated that CRFB5, a receptor shared by fish type I interferon, is a novel target of miR-30b-5p. Furthermore, it was found that miR-30b-5p can suppress post-transcriptional CRFB5 expression. Importantly, this study revealed for the first time that miR-30b-5p negatively regulates the JAK/STAT signaling pathway, thereby mediating the antiviral immune response in silver carp by targeting CRFB5 and maintaining immune system stability. These findings not only contribute to the understanding of how miRNAs act as negative feedback regulators in teleost fish antiviral immunity but also suggest their potential therapeutic measures to prevent an excessive immune response.

Downregulation of miR-1388 Regulates the Expression of Antiviral Genes via Tumor Necrosis Factor Receptor (TNFR)-Associated Factor 3 Targeting Following poly(I:C) Stimulation in Silver Carp (Hypophthalmichthys molitrix).

MicroRNAs (miRNAs) are highly conserved endogenous single-stranded non-coding RNA molecules that play a crucial role in regulating gene expression to maintain normal physiological functions in fish. Nevertheless, the specific physiological role of miRNAs in lower vertebrates, particularly in comparison to mammals, remains elusive. Additionally, the mechanisms underlying the control of antiviral responses triggered by viral stimulation in fish are still not fully understood. In this study, we investigated the regulatory impact of miR-1388 on the signaling pathway mediated by IFN regulatory factor 3 (IRF3). Our findings revealed that following stimulation with the viral analog poly(I:C), the expression of miR-1388 was significantly upregulated in primary immune tissues and macrophages. Through a dual luciferase reporter assay, we corroborated a direct targeting relationship between miR-1388 and tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3). Furthermore, our study demonstrated a distinct negative post-transcriptional correlation between miR-1388 and TRAF3. We observed a significant negative post-transcriptional regulatory association between miR-1388 and the levels of antiviral genes following poly(I:C) stimulation. Utilizing reporter plasmids, we elucidated the role of miR-1388 in the antiviral signaling pathway activated by TRAF3. By intervening with siRNA-TRAF3, we validated that miR-1388 regulates the expression of antiviral genes and the production of type I interferons (IFN-Is) through its interaction with TRAF3. Collectively, our experiments highlight the regulatory influence of miR-1388 on the IRF3-mediated signaling pathway by targeting TRAF3 post poly(I:C) stimulation. These findings provide compelling evidence for enhancing our understanding of the mechanisms through which fish miRNAs participate in immune responses.

Lovastatin/SN38 co-loaded liposomes amplified ICB therapeutic effect via remodeling the immunologically-cold colon tumor and synergized stimulation of cGAS-STING pathway.

Current immune checkpoint blockade (ICB) immunotherapeutics have revolutionized cancer treatment. However, many cancers especially the "immunologically cold" tumors, do not respond to ICB, prompting the search for additional strategies to achieve durable responses. The cGAS-STING pathway, as an essential immune response pathway, has been demonstrated for a potent target to sensitize ICB immunotherapy. However, the low efficiency of conventional STING agonists limits their clinical application. Recent studies have shown that DNA topoisomerase I (TOPI) inhibitor chemodrug SN38 can activate the cGAS-STING pathway and induce an immune response through DNA damage, while the traditional statins medication lovastatin was found to inhibit DNA damage repair, which may in turn upregulate the damaged DNA level. Herein, we have developed a liposomal carrier co-loaded with SN38 and lovastatin (SL@Lip), which can be accumulated in tumors and efficiently released SN38 and lovastatin, addressing the problem of weak solubility of these two drugs. Importantly, lovastatin can increase DNA damage and enhance the activation of cGAS-STING pathway, coordinating with SN38 chemotherapy and exhibiting the enhanced combinational immunotherapy of PD-1 antibody by remodeling the tumor microenvironment in mouse colorectal cancer of both subcutaneous and orthotopic xenograft models. Overall, this study demonstrates that lovastatin-assisted cGAS-STING stimulation mediated by liposomal delivery system significantly strengthened both chemotherapy and immunotherapy of colorectal cancer, providing a clinically translational strategy for combinational ICB therapy in the "immunologically cold" tumors.

Cocrystallization of Gefitinib Potentiate Single-Dose Oral Administration for Lung Tumor Eradication via Unbalancing the DNA Damage/Repair.

Gefitinib (GEF) is a clinical medication for the treatment of lung cancer targeting the epidermal growth factor receptor (EGFR). However, its efficacy is remarkably limited by low solubility and dissolution rates. In this study, two cocrystals of GEF with co-formers were successfully synthesized using the recrystallization method characterized via Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and 2D Nuclear Overhauser Effect Spectroscopy. The solubility and dissolution rates of cocrystals were found to be two times higher than those of free GEF. In vitro cytotoxicity studies revealed that the cocrystals enhanced the inhibition of cell proliferation and apoptosis in A549 and H1299 cells compared to free GEF. In mouse models, GEF@TSBO demonstrated targeted, safe, and effective antitumor activity with only one-dose administration. Mechanistically, the GEF cocrystals were shown to increase the cellular levels of damaged DNA, while potentially downregulating PARP, thereby impairing the DNA repair machinery and leading to an imbalance between DNA damage and restoration. These findings suggest that the cocrystallization of GEF could serve as a promising adjunct to significantly enhance the physicochemical and biopharmaceutical performance for lung cancer treatment, providing a facial strategy to improve GEF anticancer efficiency with high bioavailability that can be orally administrated with only one dose.

Development of ZnO-GO-NiO membrane for removal of lead and cadmium heavy metal ions from wastewater.

The presence of heavy metal (HM) ions, such as lead, cadmium, and chromium in industrial wastewater discharge are major contaminants that pose a risk to human health. These HMs should separate from the wastewater to ensure the reuse of the discharged water in the process and mitigate their environmental impacts. The distinctive mechanical properties of 2D graphene oxide (GO), and the antifouling characteristics of metal oxides (ZnO/NiO) nanoparticles combined to produce composites supporting special features for wastewater treatment. This study employed solution casting and phase inversion methods to synthesize PSF-based GO, ZnO-GO, and ZnO-GO-NiO mixed matrix membranes and the effects of variation in composition on the removal of lead (Pb2+) and cadmium (Cd2+) ion was examined. Several characterization techniques including X-ray diffraction analysis, scanning electron microscopy, energy dispersive X-ray, and Fourier transform infrared spectroscopy were applied to analyze the synthesized NPs and MMMs. The composite membranes were also analyzed in terms of their porosity, permeability, hydrophilicity, surface roughness, zeta potential, thermal stability, mechanical strength, and flux regeneration at various transmembrane pressures (2-3 kgcm-2), and pH value (5.5). The highest adsorption capacities were measured to be 308.16 mg g-1 and 354.80 mg g-1 for Pb (II) and Cd (II), respectively, for membrane (M4_A) having 0.3 wt% of ZnO-GO-NiO nanocomposite, at 200 mg L-1 of feed concentration and 1.60 mL min-1 of permeate flux. The Pb (II) and Cd (II) adsorption breakthrough curves were created, and the results of the experiment were compared with the data of the Thomas model.

The protective mechanism of a novel polysaccharide from Lactobacillus-fermented Nostoc commune Vauch. on attenuating cadmium-induced kidney injury in mice.

A novel polysaccharide (NCVP-F) from Lactobacillus-fermented Nostoc commune Vauch. was obtained to investigate its underlying mechanism in cadmium-induced kidney injury. Results indicated that in comparison with NCVP, NCVP-F with lower molecular weight of 365.369 kDa, exhibited higher mole percentage of Man and Glc-UA, whereas slightly lower mole percentage of other monosaccharides. NCVP-F is a α-pyran polysaccharide similar to NCVP. Meanwhile, NCVP-F can more effectively alleviate hepatorenal injury (ALT, AST, TG, BUN and SCr) and kidney tissue lesions in Cd-injured mice model by increasing antioxidant enzyme activity (SOD, GSH and GSH-Px), inhibiting cytokines levels (IL-6, IL-1ß, TNF-α and IL-18). In addition, NCVP-F effectively inhibited apoptosis proteins (Bax, cytochrome c, a-caspase-9 and a-caspase-3) and enhanced anti-apoptotic protein (Bcl-2) probably via activating PI3K/AKT/mTOR pathway in the Cd-injury kidney. Furthermore, 16S rRNA sequencing results indicated that NCVP-F better enriched Lachnospiraceae, reduced Muribaculaceae, Alloprevotella and Blautia to regulate Cd-induced gut microbiota disorders, which was probably down-regulated 7 pathways including apoptosis and lipopolysaccharide biosynthesis, and up-regulated 63 pathways, such as carbohydrate metabolism and lipid metabolism. This study suggested that applying functional NCVP-F prepared by biotransformation with low molecular weight might be more beneficial.

A scientometrics study of the nanomedicines assisted in respiratory diseases.

Nanomedicine has been extensively studied for its versatility and broad-spectrum applications of theranostics in the research of respiratory disease. However, to the best of our knowledge, a scientometrics study based on the scientific knowledge assay of the overall situation on nanomedicine applied in the research of respiratory disease has not been reported so far, which would be of major importance to relevant researchers. To explore and exhibit the research status and developing trend of nanomedicines deployed in basic or clinical research in respiratory disease, the research ecosystem and exciting subareas were profiled based on the massive data mining and visualization from the relevant works reported from 2006 to 2021. Data were collected from the Web of Science database. Data statistics software and bibliometric analysis software were employed to visualize the research trend and the relationship between respiratory diseases and nanomedicines in each representative direction. The cluster analysis and burst detections indicated that the improvement of drug delivery and vaccine developments are the up-to-date key directions in nanomedicines for respiratory disease research and treatments. Furthermore, we emphatically studied four branch areas in this field including COVID-19, nanotube, respiratory syncytial virus, and mRNA vaccine those are selected for in-depth mining and bibliometric coupling analysis. Research trends signify the future focuses will center on preventing respiratory diseases with mRNA vaccines using nanoparticle-based approaches. We anticipate our study will enable researchers to have the panorama and deep insights in this area, thus inspiriting further exploitations especially the nanobiomaterial-based systems for theranostic applications in respiratory disease treatment.

Levosulpiride for Premature Ejaculation: A Systematic Review and Meta-Analysis.

Premature ejaculation (PE) is one of the major causes of sexual dysfunction. Levosulpiride is an off-label medicine used to treat PE, but no review on its efficacy exists. A systematic review and meta-analysis was performed to determine the efficacy of levosulpiride in treating PE. Databases PubMed, Science Direct, and Google Scholar were searched. Randomized control trials (RCTs) comparing levosulpiride with placebo or other medicine were selected. Odds ratio (OR) of improved intravaginal ejaculation latency time (IELT) was calculated. A total of 97 articles were retrieved from database search, of which only four RCTs containing 203 men met the selection criteria. All four RCTs were included in systematic review while only two were included in meta-analysis. A high selection and detection bias was found in both of these studies. Meta-analysis also showed the odds of improving IELT in PE patients using levosulpiride to be significantly higher (p < .05) compared with those who used placebo, OR: 100.81, 95% confidence interval (CI) [13.12-774.90], I2 = 0%. Odds of improving IELT for > 5 min (500% improvement) were also significantly higher (p < .05) compared with the placebo groups (OR: 38.88, 95% CI [5.12-295.29], I2 = 0%). The odds of improving IELT for > 1 min, but < 5 min were also significantly higher (p < .05) than placebo groups (OR: 32.84, 95% CI [4.15-259.75], I2 = 0%). Levosulpiride improved IELT, but even so, limited studies are available on this topic. Additional research is thus required to support the present review's findings.