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This research delves into the influence of H2Valdien derivatives on the proliferation, migration, and apoptosis induction in hepatoma carcinoma cells (HepG2, Huh-7, and SMMC-7721), with a specific emphasis on inhibiting epithelial–mesenchymal transition (EMT) through modulation of the Hedgehog (Hh) signaling pathway. Utilizing the cell counting kit-8 method, flow cytometry, TUNEL assay, wound healing, and transwell assays, we observed a dose-dependent growth arrest and apoptosis induction in HepG2, Huh-7, and SMMC-7721 cells. Notably, H2Valdien derivatives exhibited a capacity to reduce migration and invasion, impacting the expression of EMT-associated proteins such as N-cadherin, vimentin, and E-cadherin. Mechanistically, these derivatives demonstrated the inhibition of the Hh signaling pathway by inactivating Sonic Hh (Shh) and smoothened proteins. This study underscores the robust antiproliferative and apoptosis-inducing effects of H2Valdien derivatives on hepatoma carcinoma cells and elucidates their regulatory role in EMT through modulation of the Hh signaling pathway, providing valuable insights for potential therapeutic interventions.

Multicentric Castleman disease (MCD) is a heterogeneous, life-threatening disease. A subgroup of HIV-negative and HHV-8-negative MCD is defined as idiopathic MCD (iMCD) with a poor prognosis. Here we report an unusual case of a 47-year-old male patient with iMCD who experienced multiple treatment regimens such as chemotherapy, immunomodulatory therapy, and targeted therapy, all of which were considered ineffective. Subsequently, he was started on bortezomib in combination with dexamethasone for six cycles and he was in complete remission. The patient has survived nearly 13 years to date – the longest survival of any iMCD patient treated with bortezomib in combination with dexamethasone. Bortezomib combined with dexamethasone may be an effective salvage strategy for severe and refractory iMCD.

Background Pressure ulcers, also called decubitus ulcers and bedsores, correspond to pressure injuries in modern medicine, which is a surgical disease manifested by tissue ulceration and necrosis due to continuous ischemia, hypoxia and malnutrition associated with long-term pressure. Moxibustion has significant clinical effect on pressure injury, but there are few relevant fundamental researches and its mechanism is still unclear. Objective To observe the effect of circling moxibustion on the ultrastructure of wound tissue in rats with pressure injury using transmission electron microscope, clarify the role of circling moxibustion in promoting wound repair, and provide a theoretical basis and reference plan for clinical moxibustion treatment of pressure injuries. Methods A total of 120 healthy female SD adult rats were selected from December 2020 to November 2021, and 85 of which were selected to establish the rat model of stage 2 or 3 pressure injury through ischemia-reperfusion injury with self-made modeling device. The 70 female SD rats with successful model preparation were randomly divided into circling moxibustion group (n=35) and model control group (n=35). Another 35 healthy female SD rats were selected as the blank control group. Each group was divided into five subgroups including the 1st, 3rd, 5th, 7th and 10th day according to the length of intervention time, with 7 rats in each subgroup. The circling moxibustion group received circling moxibustion treatment (once /d for 15 min each time) after routine iodophor intervention, while the model control group and blank control group only received routine iodophor intervention. On the 1st, 3rd, 5th, 7th and 10th day of the intervention, the rats in each subgroup were sampled and transmission electron microscope was used to observe the ultrastructure of skin tissue with pressure injury. Results The results of transmission electron microscope observation showed that the epidermis of rats was exfoliated or atrophied after modeling and the original normal skin structure was changed compared with blank control group. The model control group showed changes in the fundamental pathological state of self-repair at different time-points: 5 d subgroup showed a high infiltration stage of acute inflammation with a large number of inflammatory cells highly infiltrated which mainly belonged to neutrophils in fresh state. 10 d subgroup showed that only a small part of the epidermal structure was intact and most of the epidermal structure could not be seen, which only presented stratum basale and stratum spinosum without stratum granulosum, stratum lucidum and stratum corneum. The mitochondria of basal cells and prickle cells were still swollen, and the inflammatory cells were mainly infiltrated by apoptotic lymphocytes and phagocytes. With the accumulation of moxibustion intervention stimulation, the epidermis structure in the circling moxibustion group gradually repaired: 5 d subgroup showed that the epidermal structure was partially intact, only stratum basale and stratum spinosum could be seen partially. The complete full-thickness structures of the epidermis including stratum basale, stratum spinosum, stratum granulosum, stratum lucidum and stratum corneum existed in the 7 d subgroup. 5-10 d subgroups showed that the structure, quantity and morphology of mitochondria of basal cells and spinous cells gradually changed from the state of swelling, less quantity, less abundance and unclear structure after injury to the direction of no swelling, more quantity, abundance and clear structure after repair. The results of circling moxibustion group under the microscope of inflammatory cells showed that there were substantial neutrophils infiltrations in the 1d subgroup, which decreased to the medium amount in the 3 d subgroup with fewer inflammatory cells. Several inflammatory cells were in the state of apoptosis with obvious karyopyknosis. There were stale and old neutrophils in the 5 d subgroup, phagocytes and lymphocytes in the 7 d subgroup and lymphocytes in the 10 d subgroup. Conclusion (1) Circling moxibustion can play a significant role in promoting epidermal repair of the wound tissue in rats with pressure injury. (2) Circling moxibustion can make the peak of acute inflammatory infiltration in advance and shorten the time required for wound repair in the overall process as a whole, indicating that circling moxibustion can effectively promote the wound healing in rats with pressure injury.

The dysregulation of the intestinal epithelial barrier significantly contributes to the inflammatory progression of ulcerative colitis. Recent studies have indicated that lactate, produced by gut bacteria or derived from fermented foods, plays a key role in modulating inflammation via G-protein-coupled receptor 81 (GPR81). In this study, we aimed to investigate the potential role of GPR81 in the progression of colitis and to assess the impact of lactate/GPR81 signaling on intestinal epithelial barrier function. Our findings demonstrated a downregulation of GPR81 protein expression in patients with colitis. Functional verification experiments showed that Gpr81-deficient mice exhibited more severe damage to the intestinal epithelial barrier and increased susceptibility to DSS-induced colitis, characterized by exacerbated oxidative stress, elevated inflammatory cytokine secretion, and impaired expression of tight-junction proteins. Mechanistically, we found that lactate could suppress TNF-α-induced MMP-9 expression and prevent the disruption of tight-junction proteins by inhibiting NF-κB activation through GPR81 in vitro. Furthermore, our study showed that dietary lactate could preserve intestinal epithelial barrier function against DSS-induced damage in a GPR81-dependent manner in vivo. Collectively, these results underscore the crucial involvement of the lactate/GPR81 signaling pathway in maintaining intestinal epithelial barrier function, providing a potential therapeutic strategy for ulcerative colitis. [ABSTRACT FROM AUTHOR]

Effective signal amplification is necessary for the sensitive detection of low-abundance proteins. In this work, a sandwich-type immunosensor for the sensitive detection of alpha-fetoprotein (AFP) was prepared. Hollow mesoporous silica spheres (HMSS) with a large specific surface area and loading capacity were synthesized. Next, their adsorption performance was improved by a hyaluronic acid (HA) coating that could inhibit the escape of lead(II) ions adsorbed on the hollow silica spheres. After that, an "off–on" strategy was applied to the immunosensor to amplify δ I. The sensitive detection of AFP was obtained by square wave voltammetry (SWV). The antifouling material (HA) not only reduces non-specific binding, but also has good biocompatibility and increases the number of attached secondary antibodies. Finally, we confirmed the successful application of the "off–on" strategy by some electrochemical tests. The final electrochemical sensor has high sensitivity and a low detection limit of 9.9 fg mL−1 (S/N = 3). The proposed "metal ion (organic small molecule)-HMSS@HA" bioresponsive release system has potential application value as a carrier for other electroactive substances. [ABSTRACT FROM AUTHOR]