Background: Tibial cortex transverse transport (TTT) surgery has become an ideal treatment for patients with type 2 severe diabetic foot ulcerations (DFUs), while conventional treatments are ineffective. Based on our clinical practice experience, the protective immune response from TTT surgery may play a role against infections to promote wound healing in patients with DFUs. Therefore, this research aimed to systematically study the specific clinical efficacy and the mechanism of TTT surgery. Materials and methods: Between June 2022 and September 2023, 68 patients with type 2 severe DFUs were enrolled and therapized by TTT surgery in this cross-sectional and experimental study. Major clinical outcomes, including limb salvage rate and antibiotics usage rate, were investigated. Ten clinical characteristics and laboratory features of glucose metabolism and kidney function were statistically analyzed. Blood samples from six key time points of TTT surgery were collected for label-free proteomics and clinical immune biomarker analysis. Besides, tissue samples from three key time points were used for spatially resolved metabolomics and transcriptomics analysis, as well as applied to validate the key TTT-regulated molecules by reverse-transcription quantitative PCR. Results: Notably, 64.7% of patients did not use antibiotics during the entire TTT surgery. TTT surgery can achieve a high limb salvage rate of 92.6% in patients with unilateral or bilateral DFUs. Pathway analysis of a total of 252 differentially expressed proteins from the proteomic revealed that the immune response induced by TTT surgery at different stages was first comprehensively verified through multiomics combined with immune biomarker analysis. The function of upward transport was activating the systemic immune response, and wound healing occurs with downward transport. The spatial metabolic characteristics of skin tissue from patients with DFUs indicated downregulated levels of stearoylcarnitine and the glycerophospholipid metabolism pathway in skin tissue from patients with severe DFUs. Finally, the expressions of PRNP (prion protein) to activate the immune response, PLCB3 (phospholipase C beta 3) and VE-cadherin play roles in neovascularization, and PPDPF (pancreatic progenitor cell differentiation and proliferation factor), LAMC2 (laminin subunit gamma 2), and SPRR2G (small proline-rich protein 2G) to facilitate the developmental process mainly keratinocyte differentiation were statistically significant in skin tissues through transcriptomic and reverse-transcription quantitative PCR analysis. Conclusion: TTT surgery demonstrates favorable outcomes for patients with severe type 2 DFUs by activating a systemic immune response, contributing to anti-infection, ulcer recurrence, and the limb salvage for unilateral or bilateral DFUs. The specific clinical immune responses, candidate proteins, genes, and metabolic characteristics provide directions for in-depth mechanistic research on TTT surgery. Further research and public awareness are needed to optimize TTT surgery in patients with severe type 2 DFUs.
20 August 2025 in Frontiers in Bioengineering and Biotechnology
Cerebral ischemic stroke (CIS) is a severe cerebrovascular disease that poses numerous challenges in diagnosis and treatment, primarily attributed to blood-brain barrier (BBB) constraints and inherent drug targeting limitations. Biomimetic membrane nanotechnology, as an emerging therapeutic approach, offers a novel therapeutic strategy by emulating biological membrane structures and functions. This review comprehensively examines biomimetic nanomedicines (BMNPs) in CIS management, encompassing preparation methodologies, material characterization, and specific diagnostic/therapeutic applications. We discussed in detail various types of biomimetic nano-materials such as conventional extracellular membranes, bacterial outer membranes, and virus-like particles, and explore their capacity in enhancing BBB penetration, improving target specificity, and evading immune clearance. Current challenges regarding biosafety profiles, manufacturing quality control, targeted modification precision, and controlled drug release kinetics are delineated in this review. Looking to the future, advancing synergies between nanotechnology and biomedicine hold significant promise for optimizing CIS theranostics and expanding clinical treatment modalities.
Migraine, ranked as the second most disabling neurological disorder globally, affects over 1 billion people, imposing a substantial worldwide burden. The complexity of its pathological mechanisms contributes to therapeutic limitations. While existing first-line drugs offer partial efficacy, their utility is often constrained by cardiovascular risks, medication-overuse headaches, low bioavailability, and high treatment costs, necessitating novel therapies that balance efficacy and safety. Notably, senkyunolides, core bioactive compounds derived from traditional anti-migraine herbs like Ligusticum chuanxiong , have emerged as promising candidates due to the role of multidimensional homeostasis in regulating neurovascular units (suppressing activation of the trigeminal vascular system, modulating pathological vascular alterations, modulating neurotransmitters and receptors, inhibiting inflammatory response, antioxidant stress and analgesic effects and improving blood-brain barrier integrity) and unique pharmacokinetic advantages (small-molecule structure enabling blood-brain barrier penetration, natural origin reducing hepatorenal toxicity risks). This review systematically analyzes senkyunolides' chemical diversity, extraction methodologies, and anti-migraine pharmacological mechanisms. It further evaluates innovative solutions addressing the critical clinical translation bottleneck of instability. Beyond providing theoretical and technical foundations for developing “multi-target, low-toxicity” anti-migraine drugs, this work deepens understanding of transforming natural products into precision medicines, establishing a new paradigm for efficient and safe therapeutics. Future research must prioritize resolving formulation stability issues and rigorously advancing the clinical translation pipeline.
Esophageal cancer is a major health burden, with smoking and alcohol as preventable risk factors. Comprehensive assessments of long-term trends, disparities, and future projections remain insufficient. Using data from the Global Burden of Disease Study 2021, this observational study evaluated the burden of esophageal cancer attributable to smoking and alcohol-attributable esophageal cancer burden across 204 countries (1990-2021). Metrics included disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR). Temporal trends were assessed using estimated annual percentage change, decomposition analysis quantified drivers of burden changes, and a Bayesian age-period-cohort model projected burden to 2040. From 1990 to 2021, global deaths and DALYs increased, while ASMR and ASDR declined. Burden was uneven ; males had higher burden than females and peak burden occurring in the 65-79 age group. Geographically, ASRs declined notably in Central Asia and Latin America but rose sharply in West Africa. Middle SDI regions had the highest absolute burden; low-middle SDI regions showed increasing alcohol-attributable ASRs. Population growth and aging were primary drivers of absolute burden increases. Projections indicate continued declines in age-standardized rates, but male burden will remain higher. Despite declining age-standardized risks, smoking and alcohol remain major drivers of the global burden of esophageal cancer. Population growth and aging will further increase absolute case numbers. Projections to 2040 show continued declines in age-standardized mortality and DALY rates, yet male burden will remain substantially higher. Prevention should prioritize tobacco/alcohol control and targeted strategies for high-burden regions, males, and the elderly.