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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.

This study explores the compelling antitumor properties of VALD‐2, a synthetic Schiff base ligand known for its low toxicity. The focus is on investigating VALD‐2's protective role against cisplatin‐induced acute kidney injury (AKI) in mice, with a specific emphasis on mitigating oxidative stress and inflammation. The study involves daily intraperitoneal injections of amifostine or VALD‐2 over 7 days to establish an AKI model. Subsequently, mice were assigned to normal control, cisplatin group, cisplatin + amifostine group, and cisplatin + VALD‐2 10 mg/kg group, cisplatin + VALD‐2 20 mg/kg, and cisplatin + VALD‐2 40 mg/kg. Kidney injury is assessed through serum blood urea nitrogen (BUN) and creatinine (Cr) activity assays. Levels of inflammatory factors, tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6), in kidney tissue of mice were assessed through enzyme‐linked immunosorbent assay (ELISA). The protective effect of VALD‐2 is further examined through HE staining to observe pathological changes in kidney injury. The ultrastructural changes of renal cells and tubular epithelial cells were observed by electron microscopy under experimental conditions, indicating the effect of VALD‐2 on reversing cisplatin‐induced renal injury. The study delves into VALD‐2's protective mechanisms against cisplatin‐induced kidney injury by using western blot analysis to assess the expression levels of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and malondialdehyde (MDA) in kidney tissues. VALD‐2 demonstrates significant improvement in cisplatin‐induced AKI, as evidenced by increased BUN and Cr levels. It effectively protects kidney tissue from oxidative damage, enhancing SOD and GSH‐Px activities while reducing MDA levels. The study also reveals a decrease in TNF‐α and IL‐6 levels, supported by ELISA results, and histological findings confirm anti‐nephrotoxic effects. Western blot analysis shows an upregulation of antioxidant enzymes (SOD, GSH‐Px) and a reduction in MDA production. VALD‐2 emerges as a promising mitigator of cisplatin‐induced AKI, showcasing its ability to enhance oxidative stress‐related protein expression. The findings suggest VALD‐2 as a potential therapeutic agent for protecting against cisplatin‐induced kidney injury. Highlights: VALD‐2 is a yellow precipitate, a Schiff base ligand synthesized by mixing diethylene‐triamine and o‐vanillin and insoluble in 0.9% sodium chloride. It has been also reported that which forms complexes with most metals and has potential antibacterial, antiviral, and anticancer effects.In our previous study, we found that VALD showed antitumor effects both in vivo and in vitro. In recent years, the antitumor activities of some Schiff base ligands have been widely reported.Our study revealed for the first time that VALD‐2 alleviates cisplatin‐induced acute renal injury by inhibiting renal inflammation and enhancing the endogenous antioxidant system, which provides a molecular basis for the new drug treatment of cisplatin‐induced acute renal injury. [ABSTRACT FROM AUTHOR]