Schwann cell-like cells (SCLCs), differentiated from mesenchymal stem cells, have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies. However, certain clinical obstacles limit their application. Hence, the primary aim of this study was to investigate the role of exosomes derived from SCLCs (SCLCs-exo) in peripheral nerve regeneration. SCLCs were differentiated from human amniotic mesenchymal stem cells (hAMSCs) in vitro and validated by immunofluorescence, real-time quantitative PCR and western blot analysis. Exosomes derived from hAMSCs (hAMSCs-exo) and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis, WB analysis and electron microscopy. A prefabricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model. The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury (PNI) regeneration were determined based on the recovery of neurological function and histomorphometric variation. The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell proliferation and migration assessment. SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and S100. Compared to hAMSCs-exo, SCLCs-exo significantly enhanced motor function recovery, attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth, myelin formation and angiogenesis in the rat model. Furthermore, hAMSCs-exo and SCLCs-exo were efficiently absorbed by Schwann cells. However, compared to hAMSCs-exo, SCLCs-exo significantly promoted the proliferation and migration of Schwann cells. SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor, myelin positive regulators (SRY-box transcription factor 10, early growth response protein 2 and organic cation/carnitine transporter 6) and myelin proteins (myelin basic protein and myelin protein zero) in Schwann cells. These findings suggest that SCLCs-exo can more efficiently promote PNI regeneration than hAMSCs-exo and are a potentially novel therapeutic approach for treating PNI.

Alzheimer's disease (AD), the most prevalent human dementia, is driven by accruals of extracellular Aβ₄₂ senile patches and intracellular neurofibrillary tangles of hyperphosphorylated Tau (p-Tau) proteins. AD's concurrent neuroinflammation is prompted by innate immunity-related cytosolic protein oligomers named inflammasomes. Upon proper "first" (priming) and "second" (activating) signals, inflammasomes overproduce proinflammatory Interleukin (IL)-1β, and IL-18 while cleaving pyroptosis-promoting Gasdermin D's N-terminal fragments. Our earlier studies highlighted that in pure monocultures, exogenous Aβ_25-35-treated nonproliferating human cortical astrocytes (HCAs) made and released surpluses of endogenous Aβ₄₂-oligomers (-os) and p-Tau-os, just as alike-treated human cortical neurons did. Aβ_25-35-exposed HCAs also over-released NO, VEGFA, and IL-6. Aβ•CaSR (Aβ·Calcium-Sensing Receptor) complexes generated intracellular signals mediating all such neurotoxic effects since CaSR's negative allosteric modulators (aka NAMs or calcilytics, e.g., NPS2143) fully suppressed them. However, it had hitherto remained unexplored whether signals from Aβ·CaSR complexes also induced the early expression and/or activation of NOD-like 2 (NLRP2) and 3 (NLRP3) and of PYHIN absent in melanoma 2 (AIM2) inflammasomes in monocultured HCAs. To clarify this topic, we used in-situ-Proximity Ligation, qRT-PCR, double antibody arrays, immunoblots, and Caspase 1/4 enzymatic assays. Aβ·CaSR complexes quickly assembled on HCAs surface and issued intracellular signals activating Akt and JAK/STAT axes. In turn, the latter upregulated NLRP2 and NLRP3 PRRs (pattern recognition receptors) yet downregulated AIM2. These effects were specific, being significantly hindered by NPS2143 and inhibitors of PI3K (LY294002), AMPKα (Dorsomorphin), mTOR (Torin1), and JAK/TYK (Brepoticinib). A wide-spectrum inhibitor, Bay11-7082, intensified the Aβ·CaSR/Akt/JAK/STAT axis-driven opposite control of NLRP3's and AIM2's PRR proteins without affecting NLRP2 PRR upregulation. However, the said effects on the PRRs proteins vanished within 24-h. Moreover, Aβ·CaSR signals neither concurrently changed ASC, pro-IL-1β, and Gasdermin-D (holo- and fragments) protein levels and Caspases 1 and 4 enzymatic activities nor induced pyroptosis. Therefore, Aβ·CaSR cues acted as "first (priming) signals" temporarily increasing NLRP2 and NLRP3 PRRs expression without activating the corresponding inflammasomes. The neatly divergent modulation of NLRP3's vs. AIM2's PRR proteins by Aβ·CaSR cues and by Bay11-7082 suggests that, when bacterial or viral DNA fragments are absent, AIM2 might play "anti-inflammasomal" or other roles in HCAs. However, Bay11-7082's no effect on NLRP2 PRR overexpression also reveals that CaSR's downstream mechanisms controlling inflammasomes' sensors are quite complex in HCAs, and hence, given AD's impact on human health, well worth further studies.

Perforator flaps have been increasingly used to repair stage IV buttock pressure ulcers. However, no one has proposed an approach for stage IV buttock pressure ulcers repairing based on the subregion of buttock pressure ulcers. This study aims to evaluate the effect of perforator flaps in the repair of stage IV buttock pressure ulcers, and flap selection was based on the location of the pressure ulcers. Over the past 5 years, we evaluated 65 cases of stage IV buttock pressure ulcers repaired using perforator flaps. Flap selection was based on the subregion of each buttock pressure ulcer, following our approach. A total of 87 perforator flaps were used for 65 cases, including 42 superior gluteal artery perforator flaps, 19 fourth lumbar artery perforator flaps, and 26 descending inferior gluteal artery perforator flaps. All patients showed satisfactory reconstruction. The authors' approach can support surgeons in selecting the appropriate flaps to repair stage IV buttock pressure ulcers and achieve excellent reconstructive outcomes. This method makes the selection of flaps for pressure ulcer repair systematic, simple, and highly feasible and thus is worthy of promotion.

Background: It has been a great challenge to treat clinical stage 4 Diabetic foot ulcers (DFUs) due to high rates of major amputations and prolonged healing time. This study aimed to assess the effectiveness of a three-stage sequential surgical approach, which based on the Integrated Surgery Wound Treatment (ISWT) mode, to manage clinical stage 4 DFUs and compare the benefit of incorporating tibial cortex transverse transport (TTT) surgery at stage 3 treatment. Methods: Twenty-three patients with clinical stage 4 DFUs aged 45–75 years treated between January 2022 and February 2023 were retrospectively analyzed. Eleven patients (Group A) received wound debridement, antibiotic-loaded bone cement (ALBC) at stage 1 treatment, percutaneous transluminal angioplasty (PTA), wound debridement, and ALBC at stage 2 treatment, and skin grafting with TTT at stage 3 treatment, while twelve patients (Group B) received the same treatment without TTT. Assessed clinical outcomes included length of hospital stay, ulcer healing duration, ulcer recurrence rate, reintervention (re)-PTA rate, amputation rate, mortality rate, visual analog scale (VAS) scores, ankle-brachial index (ABI), and two-point discrimination (2-PD) ability. The computed tomographic angiography (CTA) was used to evaluate vascular hyperplasia. Results: Group A showed no occurrences of re-PTA ( P = 0.037) and similar ulcer healing times ( P = 0.975) compared to Group B. Ulcer outcome, amputation, and mortality rate were also alike in the two groups ( P > 0.05). One year after surgery, Group A demonstrated improvement in VAS scores, ABI, and 2-PD, while Group B showed no significant changes. Additionally, Group A exhibited enhanced lower limb artery characteristics compared to Group B. Conclusion: The sequential three-stage approach based on the ISWT mode effectively manages clinical stage 4 DFUs. Incorporating TTT surgery at stage 3 extends the benefits of PTA surgery.