Type 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease in young patients and is characterized by the loss of pancreatic β cells; as a result, the body becomes insulin deficient and hyperglycemic. Administration or injection of exogenous insulin cannot mimic the endogenous insulin secreted by a healthy pancreas. Pancreas and islet transplantation have emerged as promising treatments for reconstructing the normal regulation of blood glucose in T1DM patients. However, a critical shortage of pancreases and islets derived from human organ donors, complications associated with transplantations, high cost, and limited procedural availability remain bottlenecks in the widespread application of these strategies. Attempts have been directed to accommodate the increasing population of patients with T1DM. Stem cell therapy holds great potential for curing patients with T1DM. With the advent of research on stem cell therapy for various diseases, breakthroughs in stem cell-based therapy for T1DM have been reported. However, many unsolved issues need to be addressed before stem cell therapy will be clinically feasible for diabetic patients. In this review, we discuss the current research advances in strategies to obtain insulin-producing cells (IPCs) from different precursor cells and in stem cell-based therapies for diabetes.

The chemoresistance of prostate cancer (PCa) is invariably associated with the aggressiveness and metastasis of this disease. New emerging evidence indicates that the epithelial-to-mesenchymal transition (EMT) may play pivotal roles in the development of chemoresistance and metastasis. As a hallmark of EMT, E-cadherin is suggested to be a key marker in the development of chemoresistance. However, the molecular mechanisms underlying PCa chemoresistance remain unclear. The current study aimed to explore the association between EMT and chemoresistance in PCa as well as whether changing the expression of E-cadherin would affect PCa chemoresistance. Parental PC3 and DU145 cells and their chemoresistant PC3-TxR and DU145-TxR cells were analyzed. PC3-TxR and DU145-TxR cells were transfected with E-cadherin-expressing lentivirus to overexpress E-cadherin; PC3 and DU145 cells were transfected with small interfering RNA to silence E-cadherin. Changes of EMT phenotype-related markers and signaling pathways were assessed by Western blotting and quantitative real-time polymerase chain reaction. Tumor cell migration, invasion, and colony formation were then evaluated by wound healing, transwell, and colony formation assays, respectively. The drug sensitivity was evaluated using MTS assay. Chemoresistant PC3-TxR and DU145-TxR cells exhibited an invasive and metastatic phenotype that associated with EMT, including the down-regulation of E-cadherin and up-regulation of Vimentin, Snail, and N-cadherin, comparing with that of parental PC3 and DU145 cells. When E-cadherin was overexpressed in PC3-TxR and DU145-TxR cells, the expression of Vimentin and Claudin-1 was down-regulated, and tumor cell migration and invasion were inhibited. In particular, the sensitivity to paclitaxel was reactivated in E-cadherin-overexpressing PC3-TxR and DU145-TxR cells. When E-cadherin expression was silenced in parental PC3 and DU145 cells, the expression of Vimentin and Snail was up-regulated, and, particularly, the sensitivity to paclitaxel was decreased. Interestingly, Notch-1 expression was up-regulated in PC3-TxR and DU145-TxR cells, whereas the E-cadherin expression was down-regulated in these cells comparing with their parental cells. The use of γ-secretase inhibitor, a Notch signaling pathway inhibitor, significantly increased the sensitivity of chemoresistant cells to paclitaxel. The down-regulation of E-cadherin enhances PCa chemoresistance via Notch signaling, and inhibiting the Notch signaling pathway may reverse PCa chemoresistance.

Background: Prostate cancer (PCa) is still a serious male malignant disease across the world. However, no exact pathogenesis had been explained. Although adenylosuccinate lyase (ADSL) gene was identified to be important in PCa early in 1987, its comprehensive functions for PCa have not been presented. Methods: The cBioPortal for Cancer Genomics, Oncomine and GEO database were retrieved to investigate the associations between of the ADSL gene and PCa. Then, the PC-3, DU145 and C4-2B cell lines were applied in vitro experiments. RNA sequencing and further western blot (WB) were applied to explore the potential mechanisms of ADSL gene in PCa. Results: Based on PCa clinical datasets, we firstly found ADSL gene highly expressed in PCa tissues. Moreover, its transcript level increased in the metastatic PCa further. Elevated ADSL gene expression indicated a poor prognosis of PCa. While inhibiting the expression of ADSL with siRNA, the ability of cell proliferation and migration all declined markedly, with increased cell apoptosis inversely. Most of cells were blocked in the G0/G1 phase. Additionally, RNA sequencing also discovered the inactivity of cell cycle pathway after ADSL knockdown, which had also confirmed on the proteins levels. Conclusions: Our study identified the ADSL as an oncogene of PCa through regulating the cell cycle pathway firstly, with explicit cell and clinical phenotypes. Further mechanisms were needed to confirm its carcinogenic effect.

The complex pathogenesis of Alzheimer's disease (AD), combined with the presence of the blood‒brain barrier (BBB), severely limits the effectiveness of conventional therapeutic approaches. Engineered exosomes—nanoscale extracellular vesicles of natural origin—have emerged as a promising platform for innovative AD therapy due to their excellent biocompatibility, low immunogenicity and intrinsic ability to cross the BBB. This review provides a systematic overview of the synthetic and structural biological characteristics of exosomes, with a focus on their functionalisation through physical, chemical and genetic modifications. These approaches enable the targeted loading of therapeutic cargo and the conjugation of brain‐targeting peptides, thereby facilitating precise delivery to specific brain regions and offering a multi‐target therapeutic strategy for AD. We further examine the potential of engineered exosomes in modulating core AD pathological pathways, including amyloid‐beta deposition, tau hyperphosphorylation, neuroinflammation and synaptic dysfunction, and highlight their utility as an integrated delivery system for the co‐delivery of multiple therapeutic agents to achieve synergistic therapeutic effects. Finally, key challenges in clinical translation are addressed, such as scalable production, standardised drug loading protocols and comprehensive assessment of safety and immunogenicity. Unlike previous reviews that primarily focus on general engineering techniques, this article emphasises a rational design strategy tailored for multi‐target synergistic therapy and presents a comprehensive roadmap from basic research to clinical application, thereby providing both theoretical insights and practical guidance for the development of next‐generation AD treatments. Key points: A multidimensional approach combining physical, chemical, and genetic modifications equips exosomes with brain‐targeted peptides, enhancing their capability for precise brain delivery in Alzheimer's disease (AD) Engineered exosomes are designed to cross the blood‐brain barrier and provide stimuli‐responsive release of therapeutic agents, enabling simultaneous clearance of amyloid‐beta plaques and neurofibrillary tangles, and inhibition of neuroinflammation. The transition from preclinical success to early‐phase human trials is underway, with intranasal administration emerging as a promising, non‐invasive method for brain drug delivery. A well‐defined plan for clinical translation includes scalable Good Manufacturing Practice (GMP) production, rigorous safety assessments, and biomarker‐guided clinical trial design to facilitate clinical application.

The root of Averrhoa carambola L. (Oxalidaceae), a traditional Chinese medicine, was mainly used in ancient times in the treatment of urinary calculi, recurrent headache and joint pain. Our aims were to explore the potential therapeutic effect of the extract of Averrhoa carambola L. (Oxalidaceae) roots (EACR) against hepatic fibrosis in CCl₄-treated rats and to understand the underlying molecular mechanism. Six groups of male Sprague Dawley rats were treated as follows: vehicle (olive oil), CCl₄ alone, CCl₄+colchicine, CCl₄+EACR 1.0 g/kg, CCl₄+EACR 0.5 g/kg and CCl₄+EACR 0.25 g/kg. At the end of the 12^th week, biomarkers of liver function, liver fibrosis, hepatic oxidative stress and antioxidant status were assayed, and histopathological and immunohistochemical evaluation of liver tissue were conducted to investigate the liver damage and fibrosis degree. Furthermore, expressions of COL-1a1, α-SMA, TGF-β1, Smad2, smad3, Smad4 and TIMP2 were examined by qPCR and/or western blot. The expressions of apoptosis-related proteins were also detected using western blot analysis. EACR treatment markedly reduced the CCl₄-induced elevation of serum aminotransferase activities, liver fibrosis indexes, and the extent of oxidative stress. EACR treatment also significantly reduced the accumulation of collagen and the immunostaining of α-SMA, TGF-β1 and Smad2, 4 and 7 in the liver of CCl₄ treated rats. In addition, EACR treatment markedly reversed the CCl₄-induced increase in mRNA expression of COL-1a1, α-SMA, TIMP2, TGF-β1, Smad2 and Smad4 and suppressed the expressions of α-SMA, TIMP2, TGF-β1, smad2, 3 and 4, BAX and cleaved caspase-3 proteins. Meanwhile, EACR treatment also significantly elevated the mRNA expression of Smad7 and the protein expression of Smad7 and Bcl-2. These results suggest that EACR has protective activity against liver fibrosis. The anti-fibrotic activity of EACR in vivo is associated with enhanced antioxidant, apoptosis-inhibition and increased MMP-2/TIMP-2 expression ratio, and with modulation of TGF-β1/Smad signaling pathway.