Head and neck squamous cell carcinoma (HNSCC) cause approximately 95% of head and neck malignancies. Clinicopathological predictions are limited, and mitochondrial DNA (mtDNA) mutations have emerged as possible biomarkers. This systematic review and meta-analysis aimed to quantify the relative contributions of several mitochondrial genome regions to the overall mutational burden in HNSCC, thereby contextualizing their potential biological importance.

Extracellular vesicles (EVs) are nano-sized membrane-bound particles released from cells and offer promise in cell-based regenerative therapy. Preclinical research has propelled the launch of clinical trials with results from initial studies recently published. A systematic review is needed to evaluate trial designs, outcomes, product characterization and safety profiles to identify barriers and inform future research directions.

Liver tissue engineering is a rapidly advancing field aiming to address the critical shortage of donor organs and improve in vitro models for drug screening and disease modeling. Decellularized liver extracellular matrix (dLECM)-based hydrogels have emerged as a leading biomaterial platform due to their ability to preserve the native biochemical composition, microstructure, and biomechanical cues of the liver microenvironment. This systematic review aims to comprehensively evaluate the methodologies, physicochemical properties, biological performance, and translational applications of dLECM-derived hydrogels in liver tissue engineering, with a focus on fabrication protocols, functional outcomes, and challenges toward clinical implementation.

Mitochondrial function has emerged as a critical regulator of neural differentiation, yet a comprehensive understanding of its diverse roles and temporal dynamics remains elusive. This systematic review synthesizes current evidence regarding mitochondrial contributions to neural stem cell differentiation and their implications for neurodevelopmental disorders.

Exosomes, characterized by their distinctive structural and functional properties, are increasingly recognized as an important focus of research in otology, offering considerable promise for both diagnostic and therapeutic purposes. This review provides a systematic summary of the biological foundations of exosomes, with particular emphasis on their potential applications in the diagnosis and treatment of ear diseases. We begin by evaluating the translational utility of exosomes as biomarkers for the early detection of otologic diseases. We then explore the therapeutic mechanisms mediated by exosomes derived from mesenchymal stem cells (MSCs), various tissues, body fluids, and plant sources. Owing to their natural capacity to encapsulate biological cargo, exosomes represent highly promising delivery vehicles capable of efficiently transporting drugs, functional proteins, and nucleic acids to target sites within the ear, thereby offering innovative avenues for the treatment of otological conditions. Finally, this review outlines prospective research directions and critically examines the major scientific challenges that must be addressed to facilitate clinical translation.

Periodontitis is a chronic inflammatory disease that compromises the periodontium and is among the most prevalent oral conditions worldwide. Recent studies highlight exosomes - small extracellular vesicles carrying nucleic acids, lipids, metabolites, and proteins - as key mediators of intercellular communication contributing to disease progression. The objective of this review was to systematically analyze the existing scientific literature regarding the role of exosomes in the pathogenesis of periodontitis. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The study question was formulated using the Population, Intervention, Comparison, and Outcome (PICO) framework: "Do exosomes contribute to the pathogenesis of periodontitis?". A literature search was performed in PubMed and ScienceDirect databases for articles published between 2015 and 2025. Inclusion criteria were restricted to original research, written in English, involving human participants or human-derived samples that explicitly focused on exosomes in the context of periodontitis. Out of 1,000 identified records, 106 full-text articles were screened, and six met the inclusion criteria. The included studies investigated salivary, gingival, or periodontal ligament stem cell-derived exosomes and reported their roles in pyroptosis, macrophage polarization, angiogenesis, and immune modulation. Key findings demonstrated that the downregulation of exosomal miR-223-3p enhanced NLRP3-mediated pyroptosis, while exosomal miR-143-3p promoted M1 macrophage polarization via the PI3K/AKT/NF-κB signaling pathway. In addition, exosomal VEGFA regulated by miR-17-5p promoted angiogenesis, and salivary exosomes exhibited immune-related protein cargo, decreased tetraspanins (CD9, CD81), and elevated PD-L1 mRNA in advanced disease. Collectively, this review underscores the ability of exosomes to transport diverse molecular cargo and influence recipient cell behavior, highlighting their role as mediators of intercellular communication in periodontal inflammation.

With the global population aging, optimizing bone regeneration is becoming increasingly important for enhancing the quality of life among elderly individuals. Progenitor cell-based therapies, such as mesenchymal stromal cells and induced pluripotent stem cells for bone regeneration have shown challenges due to cellular senescence and the control of the differentiation processes remain significant hurdles. In particular, elevated expression of senescence markers may play a pivotal role in limiting bone regeneration. This systematic review examines how these senescence markers influence the efficacy of progenitor cell therapies and whether targeting them could improve outcomes.

Liver cirrhosis and its complications increase the risk of death associated with end-stage liver disease. Liver transplantation is an option, but the procedure may have significant morbidity and mortality risks, in addition to the shortage of liver donors. Human stem cell interventions are expected to be able to remodel injured liver tissue and to maintain liver function in people with decompensated cirrhosis. So far, results of randomised clinical trials on the effects of human stem cells in adults with decompensated cirrhosis have been inconsistent.

Obesity is an already identified risk factor for various noncommunicable diseases. Berberine is an alkaloid that has manifested a significant effect in the treatment of obesity and its complications. The aim of this systematic review and meta analysis is to evaluate the effect of berberine on obesity indices.

Maxillary sinus floor augmentation is frequently performed to increase bone height for dental implants, with stem cells suggested to boost bone regeneration. Consequently, this study aimed to assess the effects of incorporating stem cells in maxillary sinus floor augmentation. Two reviewers conducted an extensive search using a mix of controlled vocabulary (MeSH) and free-text terms to locate published systematic reviews. Searches were conducted in three major electronic databases (Medline via PubMed, Embase, and Cochrane database) up to July 2025. Initially, 250 articles were found, but only five studies met inclusion criteria for meta-analysis. The meta-analysis revealed a pooled standardized mean difference in new bone formation of 1.06 (95% confidence interval of -0.31 to 2.44). In a subgroup analysis comparing mesenchymal stem cells with autogenous bone, the pooled standardized mean difference was 0.88 (95% confidence interval of 0.34 to 1.42). The study's results indicated a positive trend towards better outcomes with the use of mesenchymal stem cells, although the effect was not statistically significant at the pooled level. Additionally, combining stem cells with xenograft may yield more favorable results compared to using autogenous bone with xenograft. These findings suggest potential clinical advantages, highlighting the need for further standardized research to verify long-term outcomes.

Gastric cancer (GC) remains a significant global health burden, with high mortality due to delayed diagnosis. Advances in microbiome profiling and artificial intelligence (AI) have opened new frontiers in non-invasive cancer risk prediction. However, the methodological landscape of AI-driven microbiome-based GC prediction remains fragmented and poorly standardized.

Critical-size bone defects in the maxillofacial region remain a major challenge. Although autografts are widely used, they are limited by donor-site morbidity and graft availability. Tissue engineering with mesenchymal stem cells, particularly buccal fat pad-derived stem cells (BFPSCs), offers a promising alternative due to their accessibility and osteogenic potential. This systematic review assesses clinical evidence on the use of BFPSCs for regenerating oro-maxillofacial bone defects in adults. A systematic search was conducted in PubMed/MEDLINE, EMBASE, and Cochrane databases for studies from January 2015 to September 2025. Inclusion criteria were in vivo human studies using BFPSCs for maxillofacial bone regeneration. Excluded were in vitro, animal studies, cell-free BFP applications, and non-original articles. Two reviewers independently screened studies; discrepancies were resolved by a senior reviewer. The level of evidence was assessed using Oxford CEBM criteria. Out of 375 identified articles, 6 clinical studies (including one randomized trial) involving 49 patients met inclusion criteria. BFPSCs were applied alone or with autologous bone. All studies reported favorable clinical and radiologic outcomes; some included histologic data confirming new bone formation. BFPSCs demonstrate promising potential for maxillofacial bone regeneration. However, high-quality studies are needed to confirm effectiveness and define standardized protocols.

Stem cell-based therapies have emerged as promising strategies for periodontal regeneration. This review systematically evaluates the efficacy and safety of stem cell-based therapies, including periodontal ligament, dental pulp, gingival, bone marrow, and other mesenchymal stem cells for advanced periodontal regeneration. The objective was to assess regenerative outcomes of stem cells compared to conventional treatments. A comprehensive literature search was conducted across databases, including PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science, plus additional sources as applicable, up to 2024 December. Studies were included if they utilized stem cell-based interventions aimed at periodontal regeneration with specified outcomes and study designs (e.g., RCTs, controlled preclinical trials). Two independent reviewers screened articles. Qualitative and quantitative analysis was done and the clinical outcomes and risk of bias were interpreted. Meta-analysis was performed using standardized mean differences (SMD) and 95% confidence intervals (PROSPERO ID.: CRD420251132434.). Nine clinical studies met inclusion. Pooled analysis demonstrated significant improvements with stem cell therapies: clinical attachment level (CAL) gain of 2.02 mm, probing depth (PD) reduction of 2.71 mm, and bone fill of 46.1%. Heterogeneity was moderate across outcomes (I2 range: 36-47%). GRADE assessment rated evidence certainty as moderate for CAL and PD, and low for bone fill. Stem cell-based approaches have great potential to transform periodontal regeneration compared with conventional methods, particularly in CAL gain, PD reduction, and bone fill. However, evidence remains limited by small sample sizes, heterogeneous protocols, and short follow-up. Well-designed, multicenter RCTs with standardized protocols and extended follow-up durations are needed to confirm the long-term efficacy and safety.

Osteonecrosis of the femoral head is a progressive disorder leading to femoral head collapse and early disability, often affecting young adults. Core decompression (CD) is the most established hip-preserving treatment for early-stage disease, yet the comparative benefits of biological and structural augmentation remain uncertain.

Graft versus host disease (GVHD) is a major drawback for haematopoietic stem cell transplant (SCT). Steroids are the main therapy. However, steroid resistance (SR) has poor outcome. Mesenchymal stromal cells (MSCs) had been assessed in several clinical trials but no consistent results. Here we present a systematic review and meta-analysis to explore the potential role of MSCs in steroid refractory acute GVHD (SR-aGVHD). We analysed 16 trials with total of 1301 patients. Primary end points included the safety of MSCs intravenous infusion (IVI), overall response rate (ORR) and overall survival (OS). Secondary end points included complete response rate (CR), relapse rate (RR) and organ specific response. Also, we analysed effect of other variables on outcome such as conditioning intensity, GVHD severity, age of recipients and MSCs related variables. ORR was 0.61 with 95% CI 0.54-0.67, CR rate was 0.29 with a 95% CI 0.23-0.36. Regarding organ specific response, Skin-ORR was 0.73, 95% CI 0.6-0.84, Gut-ORR was 0.62, 95% CI 0.54-0.7 and Liver-ORR was 0.55, 95% CI: 0.37-0.73. No statistically significant difference between the 3 organs ORR. At a median of 12 months, OS was 0.34 with 95% CI 0.29-0.4. However, in the controlled trials OS post MSCs was comparable with the control and ratio was 1.15, 95% CI of 0.81-1.62 and P = 0.4. RR was 0.10, 95% CI 0.06-0.15. Also, RR in controlled trials was comparable between MSCs recepients and control, risk ratio was 0.62, 95% CI of 0.3-1.25 and P = 0.18. Regarding heterogeniety, we assessed effect of conditioning intensity, recepients' age, GVHD severity and MSCs related variables. ORR post "MAC" was comparable with "nMAC", P = 0.7. GVHD grade IV cohorts had ORR of 0.51 while less severe GVHD had ORR 0.66 and P = 0.006. Young age (< 50 ys) was associtaed with better ORR and OS. ORR in "young" was 0.64 while older age had ORR of 0.5 and P = 0.04. And OS in "young" was 0.41 while older cohort had OS 0.25 and P = 0.04. Regarding MSCs related variables, dose of 1 × 106 cell/kg was comparable with [Formula: see text] 2 × 106 cell/kg. However, frequent MSCs infusions " [Formula: see text] 4 IVIs in first 28 days" was associated with ORR 0.64, 95% CI 0.56-0.72 while ORR in the infrequent infusions cohort was 0.47, 95% CI 0.34 - o.62 and P = 0.04. This was also translated to better survival. OS in the "Frequent" cohort was 0.4, 95% CI 0.35-0.45 while OS in the "Infrequent" cohort was 0.22, 95% CI 0.17-0.28 and P < 0.0001. Otherwise, once weekly MSCs infusion was equivalent to twice weekly and ORR post cryopreserved MSCs was comparable with fresh cells. MSCs IVI is a safe effective therapeutic modality for SR-aGVHD. Dose of 1 × 106 cell/kg and frequency of 4 or more IVI within first 4 weeks seem the optimal conditions.

Liver fibrosis is known as a condition characterized by chronic inflammation and excessive extracellular matrix deposition that causes cirrhosis and liver failure. Stem cell therapy is a promising strategy for the management of liver fibrosis because it not only improves tissue regeneration but also modulates by immunomodulatory mechanisms. This systematic review aimed to evaluate the immunoregulatory effects of stem cells in both experimental models and clinical studies of liver fibrosis. A total of 29 studies were included, comprising several stem cell sources, including bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord-derived MSCs (UC-MSCs), adipose tissue-derived MSCs (AT-MSCs), and stem cells from human exfoliated deciduous teeth (SHED), among others. Studies reported that stem cells could decrease proinflammatory cytokines (e.g., TNF-α, IFN-γ, IL-17) and fibrosis-related markers, while increasing levels of anti-inflammatory cytokines (e.g., IL-10, IL-4) and regulatory immune cells such as Tregs (regulatory T cells). Stem cells could affect immune homeostasis via modulating in macrophage polarization, T cell subsets, and B cell activity, resulting in attenuated fibrotic progression and improved liver function. Despite variability in cell types, routes of administration, and fibrosis models, the results support the potential of stem cell therapy to reform the hepatic immune microenvironment. However, more standardized protocols and clinical validations are required. This study emphasizes the immunomodulatory potential of stem cells as a therapeutic method in liver fibrosis. It brings a clear view into their mechanisms of action and the foundation for future translational applications.

Autologous fat grafting has become an important tool in reconstructive and aesthetic surgery, particularly for breast reconstruction and soft tissue augmentation. Despite its promise, long-term outcomes remain unpredictable. To address this, research has increasingly focused on optimizing graft survival by enriching the lipoaspirate with additional substances. A systematic search of PubMed and Web of Science identified studies on enhancement methods of autologous fat grafting in both animal models and clinical settings, published up to February 2025. In vitro trials, case reports, and studies comparing techniques without specific enhancement of the lipoaspirate were excluded. Twenty-seven studies fulfilled the criteria, including 15 animal studies and 12 clinical studies, most of which investigated applications in breast reconstruction and augmentation. The included studies showed substantial heterogeneity in enhancement strategies, case numbers, follow-up duration, and outcome measures. The most frequently examined approaches involved enrichment with stromal vascular fraction (SVF) and/or adipose-derived stem cells (ADSCs). Both methods demonstrated favorable results in many trials, though statistical significance was not always achieved. Other strategies included the use of Vitamin D3, Botulinum toxin A, platelet-rich plasma (PRP), and less frequently studied agents such as N-acetylcysteine and Salvia miltiorrhiza. Overall, enrichment of lipoaspirate appears to enhance graft survival, with SVF/ADSC-based methods and PRP emerging as the most promising approaches. Nevertheless, marked variability in protocols and outcome measures hampers comparability between studies. Larger randomized controlled trials employing standardized methodologies are essential to confirm clinical feasibility and provide a basis for evidence-based guidelines.

Colon Adenocarcinoma (COAD) is the second leading cause of cancer-related death worldwide, with a rising incidence. Apoptosis is a key contributor to cancer, serving as a prognostic and diagnostic marker. BID, as a link between extrinsic and intrinsic apoptosis pathways, may play an important role in COAD development.

Dental mesenchymal stem cells (DMSCs) are increasingly recognized for their regenerative properties, particularly in the context of pulp regeneration. Among the various treatment's diode laser irradiation, has gained more attention for its potential to promote stem cell differentiation, particularly osteogenic differentiation. To evaluate the effect of diode laser irradiation on the proliferation and osteogenic differentiation of dental tissue-derived mesenchymal stem cells. A comprehensive search was performed between January 2025 to June 2025 across five databases including PubMed, Cochrane Library, LILACA, Google scholar and ScienceDirect. Only in vitro studies that assessed cellular or osteogenic differentiation of DMSCS were included. The risk of bias for was assessed using the QUIN tool. A total of 21 studies were included in the review, encompassing various DMSC types, The studies explored a range of diode laser wavelengths (420-980 nm) and energy densities. Findings indicate that diode laser irradiation, particularly at wavelengths of 660 nm, 810 nm, and 980 nm, promotes osteogenic differentiation by enhancing the expression of osteogenic markers such as RUNX2, ALP, and OCN. The effect of diode laser irradiation on stem cell proliferation and osteogenic differentiation was found to be dose-dependent, with lower energy densities promoting proliferation and higher energy densities favoring differentiation. Diode laser irradiation at wavelengths of 660 nm, 810 nm, and 980 nm demonstrates potential for enhancing osteogenic differentiation of DMSCs. However, variability in laser parameters led to inconsistencies in the results, and no consensus could be reached regarding the optimal laser settings for maximum differentiation efficiency.

Mutations in Fused in Sarcoma (FUS) are associated with neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This systematic review examined the connections between DNA damage in the central nervous system (CNS), dysfunction of DNA repair processes and the FUS proteinopathy. Twelve peer-reviewed publications were analyzed, investigating this question across a range of models, including immortalized cell lines, ALS-FTD patient-derived induced pluripotent stem cells, mouse tissues and post-mortem samples from ALS-FTD patients. The studies also explored the impact of inducing DNA damage using several agents, including calicheamicin and etoposide, on FUS pathology. Our findings indicated that accumulated DNA damage was documented in all twelve studies, with a key finding being the disruption of interactions between FUS and the DNA damage response (DDR). FUS interactions with various DDR and DNA repair proteins involved in sensing DNA damage and executing the major repair pathways were impaired, resulting in elevated levels of DNA damage in both the nucleus and mitochondria. Therefore, FUS is an essential protein for the preservation of genomic integrity and this loss of genome stability is likely to be a key contributor to the neurodegeneration in ALS-FTD.