Effectiveness and mechanisms of mesenchymal stem cell therapy in preclinical animal models of hepatic fibrosis: a systematic review and meta-analysis.

Background: Liver damage due to long-term viral infection, alcohol consumption, autoimmune decline, and other factors could lead to the gradual development of liver fibrosis. Unfortunately, until now, there has been no effective treatment for liver fibrosis. Mesenchymal stem cells, as a promising new therapy for liver fibrosis, can slow the progression of fibrosis by migrating to the site of liver injury and by altering the microenvironment of the fibrotic area. Aim: By including all relevant studies to date to comprehensively assess the efficacy of mesenchymal stem cells for the treatment of hepatic fibrosis and to explore considerations for clinical translation and therapeutic mechanisms. Methods: Data sources included PubMed, Web of Science, Embase, and Cochrane Library, and were constructed until October 2023. Data for each study outcome indicator were extracted for comprehensive analysis. Results: The overall meta-analysis showed that mesenchymal stem cells significantly improved liver function. Moreover, it inhibited the expression level of transforming growth factor-ß [SMD = 4.21, 95% CI (3.02,5.40)], which in turn silenced hepatic stellate cells and significantly reduced the area of liver fibrosis [SMD = 3.61, 95% CI (1.41,5.81)]. Conclusion: Several outcome indicators suggest that mesenchymal stem cells therapy is relatively reliable in the treatment of liver fibrosis. The therapeutic effect is cell dose-dependent over a range of doses, but not more effective at higher doses. Bone-marrow derived mesenchymal stem cells were more effective in treating liver fibrosis than mesenchymal stem cells from other sources. Systematic Review Registration: Identifier CRD42022354768.

Single and combined strategies for mesenchymal stem cell exosomes alleviate liver fibrosis: a systematic review and meta-analysis of preclinical animal models.

Background: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been supported by various clinical studies. However, stem cell transplantation is limited in clinical application due to its low survival rate, low liver implantation rate, and possible carcinogenicity. Recently, there has been increasing interest in the use of MSC-exos due to their widespread availability, low immunogenicity, and non-carcinogenic properties. Numerous studies have demonstrated the potential of MSC-exos in treating liver fibrosis and preventing progression to end-stage liver disease. Objective: This study aimed to systematically investigate the efficacy of MSC-exos single administration in the treatment of hepatic fibrosis and the combined advantages of MSC-exos in combination with drug therapy (MSC-exos-drugs). Methods: Data sources included PubMed, Web of Science, Embase, and the Cochrane Library, which were built up to January 2024. The population, intervention, comparison, outcomes, and study design (PICOS) principle was used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Results: After screening, a total of 18 papers (19 studies) were included, of which 12 involved MSC-exos single administration for the treatment of liver fibrosis and 6 involved MSC-exos-drugs for the treatment of liver fibrosis. Pooled analysis revealed that MSC-exos significantly improved liver function, promoted the repair of damaged liver tissue, and slowed the progression of hepatic fibrosis and that MSC-exos-drugs were more efficacious than MSC-exos single administration. Subgroup analyses revealed that the use of AD-MSC-exos resulted in more consistent and significant efficacy when MSC-exos was used to treat hepatic fibrosis. For MSC-exos-drugs, a more stable end result is obtained by kit extraction. Similarly, infusion through the abdominal cavity is more effective. Conclusion: The results suggest that MSC-exos can effectively treat liver fibrosis and that MSC-exos-drugs are more effective than MSC-exos single administration. Although the results of the subgroup analyses provide recommendations for clinical treatment, a large number of high-quality experimental validations are still needed. Systematic Review Registration: CRD42024516199.

Efficacy and safety of mesenchymal stem cells therapy in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the manifestation of COVID-19 symptoms, such as lung tissue edema, lung diffusion dysfunction, acute respiratory distress syndrome (ARDS), secondary infection, and ultimately mortality. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory properties, thus providing a potential treatment option for COVID-19. The number of clinical trials of MSCs for COVID-19 has been rising. However, the treatment protocols and therapeutic effects of MSCs for COVID-19 patients are inconsistent. This meta-analysis was performed to systematically determine the safety and efficacy of MSC infusion in COVID-19 patients. METHODS: We conducted a comprehensive literature search from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up to 22 November 2023 to screen for eligible randomized controlled trials. Inclusion and exclusion criteria for searched literature were formulated according to the PICOS principle, followed by the use of literature quality assessment tools to assess the risk of bias. Finally, outcome measurements including therapeutic efficacy, clinical symptoms, and adverse events of each study were extracted for statistical analysis. RESULTS: A total of 14 randomized controlled trials were collected. The results of enrolled studies demonstrated that patients with COVID-19 pneumonia who received MSC inoculation showed a decreased mortality compared with counterparts who received conventional treatment (RR: 0.76; 95% CI [0.60, 0.96]; p = 0.02). Reciprocally, MSC inoculation improved the clinical symptoms in patients (RR: 1.28; 95% CI [1.06, 1.55]; p = 0.009). In terms of immune biomarkers, MSC treatment inhibited inflammation responses in COVID-19 patients, as was indicated by the decreased levels of CRP and IL-6. Importantly, our results showed that no significant differences in the incidence of adverse reactions or serious adverse events were monitored in patients after MSC inoculation. CONCLUSION: This meta-analysis demonstrated that MSC inoculation is effective and safe in the treatment of patients with COVID-19 pneumonia. Without increasing the incidence of adverse events or serious adverse events, MSC treatment decreased patient mortality and inflammatory levels and improved the clinical symptoms in COVID-19 patients. However, large-cohort randomized controlled trials with expanded numbers of patients are required to further confirm our results.

Efficacy and safety of mesenchymal stem cell therapy in liver cirrhosis: a systematic review and meta-analysis.

AIM: Although the efficacy and safety of mesenchymal stem cell therapy for liver cirrhosis have been demonstrated in several studies. Clinical cases of mesenchymal stem cell therapy for patients with liver cirrhosis are limited and these studies lack the consistency of treatment effects. This article aimed to systematically investigate the efficacy and safety of mesenchymal stem cells in the treatment of liver cirrhosis. METHOD: The data source included PubMed/Medline, Web of Science, EMBASE, and Cochrane Library, from inception to May 2023. Literature was screened by the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Outcome indicators of the assessment included liver functions and adverse events. Statistical analysis was performed using Review Manager 5.4. RESULTS: A total of 11 clinical trials met the selection criteria. The pooled analysis' findings demonstrated that both primary and secondary indicators had improved. Compared to the control group, infusion of mesenchymal stem cells significantly increased ALB levels in 2 weeks, 1 month, 3 months, and 6 months, and significantly decreased MELD score in 1 month, 2 months, and 6 months, according to a subgroup analysis using a random-effects model. Additionally, the hepatic arterial injection favored improvements in MELD score and ALB levels. Importantly, none of the included studies indicated any severe adverse effects. CONCLUSION: The results showed that mesenchymal stem cell was effective and safe in the treatment of liver cirrhosis, improving liver function (such as a decrease in MELD score and an increase in ALB levels) in patients with liver cirrhosis and exerting protective effects on complications of liver cirrhosis and the incidence of hepatocellular carcinoma. Although the results of the subgroup analysis were informative for the selection of mesenchymal stem cells for clinical treatment, a large number of high-quality randomized controlled trials validations are still needed.

A rare case of adult colocolic intussusception secondary to splenosis.

Intussusception is the invagination of a segment of bowel (intussusceptum) into the lumen of an adjacent segment (intussuscipiens). Adult intussusception is rare and typically asymptomatic, although bowel obstruction can be a predominant symptom, making it difficult to diagnose. Splenosis is an uncommon and benign disease, arising from the self-implantation of splenic tissue elsewhere in the body after splenectomy or splenic trauma. Colocolic intussusception secondary to splenosis is rare. We report a case of colon intussusception with a mass in the intussusception detected by ultrasound. Abdominal ultrasound identified the intussusception location but failed to distinguish its pathological properties. Colonoscopy revealed the exudation of necrotic and fibrous tissue. Surgery was performed because of suspicions of a malignant tumor.

Long non-coding RNA SNHG14 exerts oncogenic functions in non-small cell lung cancer through acting as an miR-340 sponge.

Long non-coding RNA (lncRNA) SNHG14 is previously found to be overexpressed in several types of cancers. However, the clinical significance and biological function of SNHG14 in non-small cell lung cancer (NSCLC) are still elusive. In the present study, we found that SNHG14 was aberrantly up-regulated in NSCLC tissues from patients and cell lines compared with their normal counterparts. Increased SNHG14 expression was closely associated with aggressive tumor progression and poor clinical outcome of NSCLC patients. Knockdown of SNHG14 inhibited NSCLC cell proliferation through inducing cell cycle arrest and apoptosis, whereas SNHG14 overexpression exerted the opposite effects. Animal experiment further revealed that down-regulated SNHG14 greatly inhibited NSCLC tumor growth in vivo Further studies demonstrated that SNHG14 might serve as a competing endogenous RNA (ceRNA) by sponging miR-340 in NSCLC cells. Taken together, our study demonstrated that SNHG14/miR-340 axis might play a novel role in regulating the malignant behaviors of NSCLC, which provided a new potential diagnostic and therapeutic strategy for this malignant disease.

Oral Contrast-Enhanced Gastric Ultrasonography in the Assessment of Gastric Lesions: A Large-Scale Multicenter Study.

OBJECTIVE: To determine the diagnostic efficiency of oral contrast-enhanced gastric ultrasonography in the evaluation of gastric lesions, based on large-scale multicenter study. METHODS: The study enrolled 383,945 patients with suspect gastric lesions who underwent complete oral contrast-enhanced gastric ultrasonography and endoscopic evaluation. Two operators, unaware of the results of other diagnostic procedures, performed each examination independently. The accuracies of conventional ultrasonography, oral contrast-enhanced gastric ultrasonography, and upper gastrointestinal endoscopy were determined. RESULTS: After oral contrast, the anatomy of the stomach and morphologic features of gastric lesions were clearly visualized. The sensitivities, specificities, positive predictive values, negative predictive values and accuracies of oral contrast-enhanced ultrasonography in detecting the sites, sizes, numbers, and the extent of gastric lesions,were similar to those of upper gastrointestinal endoscopy (P > .05) and far greater than those of conventional ultrasonography (P < .01). Moreover, oral contrast-enhanced ultrasonography was far better than upper gastrointestinal endoscopy (P < .01) and was better than conventional ultrasonography (P < .05) in detecting the submucosal abnormalities (<5mm) and the adjacent structures abnormalities identified in surgical pathology. However, oral contrast-enhanced ultrasonography was a bit poorer than upper gastrointestinal endoscopy (P < .05) and far better than conventional ultrasonography (P < .01) in detecting the minor mucosal abnormalities (<5mm). CONCLUSION: Oral contrast-enhanced gastric ultrasonography is superior to conventional gastric ultrasonography in defining the anatomic location and extension of gastric lesions. Its diagnostic performance is not worse than upper gastrointestinal endoscopy and it can be used as a useful supplement to upper gastrointestinal endoscopy.

Environmental survey of Legionella pneumophila in hot springs in Taiwan.

Acquisition of sporadic community-acquired legionnaires' disease has been linked to hot springs and whirlpool baths. Outbreaks of hot spring-associated legionnaires' disease were reported in Japan in the last few years. Although the mode of transmission is unclear, the presence of Legionella in hot springs may discourage hot springs resort visits by the general public. An environmental survey was conducted to determine the presence of Legionella in hot springs in Taiwan. In total, 55 water samples were collected from 19 hot springs resorts; 21% (4/19) of the hot spring resorts sampled yielded L. pneumophila in the public hot springs bath. Legionella pneumophila serogroups 1 and 6, L. pneumophila serogroup 3, L. pneumophila serogroup 5, and L. pneumophila serogroup 7 were isolated from four different resort spas, respectively. The total sample positivity rate for L. pneumophila was 11% (6/55). The risk of occurrences of legionnaires' disease outbreaks associated with hot springs water in general public is unknown, and epidemiologic investigations should be conducted for locating the potential sources of Legionella for those cases of community-acquired legionnaires' disease. Disinfection of hot springs for Legionella may be necessary if the risk of contracting legionnaires' disease from hot springs can be validated by an evidence-based approach.