Pyroptosis is an emerging form of inflammatory programmed cell death primarily mediated by the gasdermin protein family, characterized by cell swelling, membrane pore formation, and the release of pro-inflammatory cytokines such as IL-1β and IL-18. This mode of cell death has garnered significant attention due to its critical involvement in a variety of diseases, including cancer, cardiovascular disorders, autoimmune diseases, and metabolic syndromes, positioning it as a promising therapeutic target. Despite advances, the complexity of pyroptosis regulation and its dual roles in disease pathogenesis present challenges that necessitate comprehensive understanding. This review systematically summarizes the molecular regulatory mechanisms of pyroptosis, encompassing classical and non-classical inflammasome pathways, activation and modulation of gasdermin proteins, and the intricate signaling networks involved. We further highlight the dualistic roles of pyroptosis in tumor development, immune modulation, and chronic inflammatory conditions. Incorporating the latest research progress, we explore emerging therapeutic strategies targeting pyroptosis, including small molecule inhibitors, nanomaterials, stem cell-derived exosomes, and gene regulation technologies, critically evaluating their clinical applicability and limitations. By providing an integrative overview of pyroptosis-related mechanisms and innovative treatment approaches, this article aims to offer a theoretical foundation and future research direction for precision medicine and novel drug development.

BACKGROUND:Clinical N0 lung cancer is surgically treated using a variety of approaches. Nevertheless, a comparison of the effectiveness of these approaches in evaluating lymph node (LN) remains to be conducted. OBJECTIVE:To evaluate the upgrading rate of LN staging, the total number of resected LNs, and the number of resected LN stations in clinical N0 lung cancer among four surgical approaches. METHODS:A comprehensive search was conducted across the PubMed, EMBASE, MEDLINE, and CENTRAL databases, encompassing papers published between 1 January 2005, and 31 March 2025. The pooled effect size was measured using odds ratios (ORs) or standardized mean differences (SMDs), as well as 95% confidence intervals (CIs). The surface under the cumulative ranking curve (SUCRA) was utilized to calculate the cumulative probability for each approach. In order to investigate the origins of heterogeneity, meta-regression and subgroup analyses were employed. RESULTS:A total of 71 070 participants from 30 studies were included in the analysis. The incidence of cN0-pN1 was higher in the open thoracotomy (OPEN) group than in the robot-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) groups [OR = 0.53 (0.32, 0.89), OR = 0.36 (0.26, 0.51), respectively]. OPEN had the highest SUCRA (97.7%), followed by RATS (59.5%) and VATS (27.3%). Regarding cN0-pN2, both the OPEN and RATS groups exhibited a higher incidence than the VATS group [OR = 0.39 (0.16, 0.91), OR = 0.20 (0.06, 0.64), respectively] with RATS demonstrating the greatest SUCRA (92.3%), followed by OPEN (56.8%) and VATS (0.9%). The video-assisted mediastinoscopic lymphadenectomy plus video-assisted thoracoscopic surgery (VM + VATS) group removed more total LNs than the VATS group [SMD = 6.66 (1.54, 11.77)], with VM + VATS having the highest SUCRA (97.7%), followed by RATS (57.8%), OPEN (44.1%), and VATS (0.4%). Heterogeneity was evident in cN0-pN2 and total LNs. Regression analysis revealed that sample size could explain some of the heterogeneity observed in cN0-pN2 [coef = 0.62 (0.04-1.26)], whereas sample size, publication year, and surgical area could explain some of the heterogeneity observed in total LNs [coef = - 21.3 (-42.03-4.23), coef = - 21.02 (-42.26-3.25), coef = - 12.54 (-31.59-3.70), respectively]. Subgroup analysis supported the previous findings. CONCLUSIONS:In terms of nodal upstaging incidence for cN0-pN1 and cN0-pN2, both OPEN and RATS performed well. For N1 lymph node (LN) resection, the OPEN approach is superior to the RATS and VATS approaches, whereas for N2, the RATS approach is superior to the OPEN and VATS approaches. Regarding the total number of LNs removed, the video-assisted mediastinoscopic lymphadenectomy (VM) + VATS and OPEN have obvious advantages. The publication year, sample size, and surgical area affected the incidence of cN0-pN2 and the total number of LNs removed. These findings may help thoracic surgeons to select different surgical approaches for patients with clinical N0 lung cancer and different tendencies for LN metastasis.

Lung cancer is a refractory malignancy. Although various therapeutic options, including targeted therapies, immune checkpoint inhibitors, and systemic chemotherapy, have significantly improved the prognosis of lung cancer patients, five-year survival rates are still low. Bispecific antibodies have attracted much attention because of their ability to bind different antigens or epitopes on the same antigen at once and because of their multiple novel functional mechanisms. Recently, three bispecific antibodies have been successively approved for lung cancer treatment, demonstrating the potential of bispecific drugs in lung cancer therapy. Various bispecific antibodies are currently under clinical trials to evaluate their safety and efficacy in lung cancer. In this review, we provide an overview of these antibodies’ structure and mechanism of action, summarize their clinical progress in lung cancer treatment, and discuss and analyze the challenges and future directions of bsAbs application in lung cancer.

This study aimed to compare perioperative features of lung cancer patients admitted via different routes and their short-term prognosis impact. A retrospective analysis included 116 consecutive patients transferred from other departments for video-assisted thoracoscopic surgery (VATS) from June 2021 - June 2024 and 353 outpatients who underwent VATS during the same period. A total of 218 patients were obtained through propensity score matching (1:1), including 109 patients in the transferred lung cancer group and 109 patients in the outpatient lung cancer group. Perioperative characteristics and short-term prognosis were compared with multivariate binary logistic regression for risk factors. A significant proportion of lung cancer patients transferred from the Department of Respiratory Medicine to the Department of Thoracic Surgery for surgical resection exhibited more complex clinical profiles than their outpatient counterparts. These patients were generally older, with poorer lung function, more advanced tumor stages, higher ASA, hypoplastic interlobar fissures, and severe pleural adhesions.​During the perioperative period, transferred patients had a higher incidence of postoperative pulmonary infections, longer hospital stays, greater hospitalization costs, and a higher 30-day readmission rate. Multivariate regression analysis identified two independent risk factors for postoperative pulmonary infection in the transferred group: longer operation time (OR = 1.011, 95

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P<0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23-5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28-4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.

Background: Knee osteoarthritis (KOA) is on the rise due to lifestyle changes, obesity, and aging, yet effective treatments are lacking. Traditional Chinese manual therapy (Tuina) is promising for KOA. However, its mechanism remains unclear. Objective: This study aims to determine the effects of Tuina on a rat KOA model, focusing on the role of chondrocyte apoptosis and autophagy mechanisms. Methods: KOA was induced in rats by intra-articular injection of L-cysteine-activated papain into the right knee. Thirty-six male Sprague Dawley (SD) rats were randomly divided into blank, model control, Tuina, and positive drug groups. Paw withdrawal threshold tests, knee joint swelling, and passive range of motion assessed knee behavior. Cartilage tissue cytology, cytokine contents, and the mRNA and protein expression of PI3K/AKT/mTOR signaling pathway components were analyzed using HE and TUNEL staining, ELISA, RT-qPCR, and Western blotting, respectively. In addition, we used machine learning methods to conduct a secondary analysis of the dataset from the in vivo experiments in rats to verify the findings. Results: Tuina significantly relieved pain and joint swelling, and improved range of motion. Staining showed reduced articular cartilage destruction and apoptosis. Tuina reduced the serum levels of IL-1 beta, IL-17, MMP-3, and MMP-13. Tuina downregulated Bax, ULK1, Beclin-1, LC3-II/I and upregulated PI3K, AKT, mTOR, and BCL-2 in cartilage tissue. The machine learning results indicated an 83.33% accuracy for the prediction model, remaining stable through both uni- and multivariate analyses. Tuina yielded the best comprehensive efficacy on KOA as well as better rat behavior and PI3K/AKT/mTOR signaling pathway improvement effect than positive drugs, while its cytokine-reducing ability was comparable to that of positive drugs. Conclusion: Tuina can alleviate cartilage tissue injury in KOA, relieve inflammation, and reduce chondrocyte apoptosis and autophagy, the underlying mechanisms of which may be associated with activation of the PI3K/AKT/mTOR signaling pathway.

Thoracoscopic lobectomy is a common surgical procedure for the treatment of lung cancer. With the continuous development of surgical techniques and medical devices, complications after thoracoscopic lobectomy are less and less, and cardiac tamponade is even rarer. This case is a 62-year-old woman who underwent thoracoscopic left upper lobectomy for a left upper lobe nodule. The patient developed acute cardiac tamponade on postoperative day 2, and symptoms resolved after pericardiocentesis. However, 20 h later, the patient underwent emergency surgery for re-developed acute cardiac tamponade, which was found to be a coronary tear. A review of the literature suggested that cardiac tamponade is more common in left lung surgery than right lung surgery. Pericardiocentesis can resolve initial acute cardiac tamponade, but pericardiotomy may be urgently needed after recurrence.

Major depressive disorder is a global psychiatric condition characterized by persistent low mood and anhedonia, which seriously jeopardizes the physical and mental well-being of affected individuals. While various hypotheses have been proposed to explicate the etiology of depression, the precise pathogenesis and effective treatment of this disorder remain elusive. Mitochondria, as the primary organelles responsible for cellular energy production, possess the ability to meet the essential energy demands of the brain. Research indicated that the accumulation of damaged mitochondria is associated with the onset of depression. Mitophagy, a type of cellular autophagy, specifically targets and removes excess or damaged mitochondria. Emerging evidence demonstrated that mitophagy dysfunction was involved in the progression of depression, and several pharmacological interventions that stimulating mitophagy exerted excellent antidepressant actions. We provided an overview of updated advancements on the regulatory mechanism of mitophagy and the mitophagy abnormality in depressed patients and animals, as well as in cell models of depression. Meanwhile, various therapeutic strategies to restore mitophagy for depression alleviation were also discussed in this review.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.

The present study aims to investigate the cognition‐enhancing effect of 3, 14, 19‐Triacetyl andrographolide (ADA) on learning and memory deficits in 3 × Tg‐AD mice and to explore its underlying mechanism. Eight‐month‐old 3 × Tg‐AD mice and C57BL/6J mice were randomly divided into three groups, namely wild‐type group, 3 × Tg‐AD group, and 3 × Tg‐AD+ADA group (5 mg/kg, for 21 days, i.p.). We found that ADA significantly improved learning and cognition impairment, inhibited the loss of Nissl body, and reduced Aβ load in the brains of 3 × Tg‐AD mice. In addition, ADA enhanced the levels of PSD95 and SYP, which were closely associated with synaptic plasticity. Accumulated autophagosomes, LC3II, and P62 in hippocampus and cortex of 3 × Tg‐AD mice were decreased by ADA treatment. Furthermore, ADA administration further down‐regulated the expressions of p‐AKT and p‐mTOR, reduced the level of CTSB, and increased the co‐localization of LC3 and LAMP1 in the brains of 3 × Tg‐AD mice, implying that ADA‐induced autophagy initiation and also promoted the degradation process. In Aβ25–35‐induced HT22 cells, ADA displayed similar effects on autophagy flux as observed in 3 × Tg‐AD mice. Our finding verified that ADA could improve synaptic plasticity and cognitive function, which is mainly attributed to the key roles of ADA in autophagy induction and degradation.

By using bioinformatics analysis and the experimental techniques of cell biology and molecular biology, we found that DEP domain-containing protein 1B (DEPDC1B) can promote the invasion and migration of breast cancer cells and that DEPDC1B mediates the deubiquitination of β-catenin by ubiquitin-specific protease 5 (USP5), thus activating the wnt/β-catenin pathway. Our findings provide new insights into the carcinogenic mechanism of DEPDC1B, suggesting that DEPDC1B can be used as a potential therapeutic target for breast cancer.

Background: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and mitophagy deficit was identified as the typical abnormality in early stage of AD. The neuroprotective effect of andrographolide (AGA) has been confirmed, anda acetylated derivative of AGA (3,14,19-triacetylandrographolide, ADA) was considered to have stronger efficacy. Purpose: The current study aims to investigate the impact of ADA on cognitive ability in a sporadic AD model and explore its potential mechanism. Study design/ methods: Apoe4 mouse was adopted for evaluating the impact of AGA on cognitive impairment through a serious of behavioral tests. The molecular mechanism of ADA involved in mitophagy and neuroinflammation was investigated in detailby Western blot, ELISA, immunofluorescence and transmission electron microscopy in Apoe4 mice, as well as Apoe4-transfected BV2 cells and HT22 cells. Results: ADA application significantly improved cognitive impairment of Apoe4 mice, and lessened A beta load and neuronal damage, which has stronger activity than its prototype AGA. Accumulated mitophagy markers LC3II, P62, TOM20, PINK1 and Parkin, and decreased mitophagy receptor BNIP3 in hippocampus of Apoe4 mice were greatly reversed after ADA treatment. Meanwhile, ADA promoted the recruitment of BNIP3 to mitochondria, and the transport of damaged mitochondria to lysosome, indicating that disturbed mitophagy in AD mice was restored by ADA. Inhibited SIRT3 and FOXO3a in Apoe4 mice brains were elevated after ADA treatment. ADA also lightened the neuroinflammation caused by NLRP3 inflammasome activation. Additionally, damaged mitophagy and/or activated NLRP3 inflammasome were also observed in BV2 cells and HT22 cells transfected with Apoe4, all of which were rescued by ADA incubation. Noteworthily, SIRT3 inhibitor 3-TYP could abolish the impact of ADA on mitophagy and NLRP3 inflammasome in vitro. Conclusion: ADA exerted stronger cognition-enhancing ability in relative to AGA, and ADA could repaire mitophagy deficiency via SIRT3-FOXO3a pathway, and subsequently inhibite NLRP3 inflammasome to mitigate AD pathology.

Background: Alzheimer's disease (AD) represents the common neurodegenerative disease featured by the manifestations of cognitive impairment and memory loss. AD could be alleviated with medication and improving quality of life. Clinical treatment of AD is mainly aimed at improving the cognitive function of patients. Donepezil, memantine and galantamine are commonly used drug. But they could only relieve AD, not cure it. Therefore, new treatment strategies focusing on AD pathogenesis are of great significance and value. Myricetin (Myr) is a natural flavonoid extracted from Myrica rubra. And it shows different bioactivities, such as anti-inflammation, antioxidation as well as central nervous system (CNS) activities. Nonetheless, its associated mechanism in treating AD remains unknown. Purpose: Here we focused on investigating Myr's effect on treating AD and exploring if its protection on the nervous system activity was associated with specifically inhibiting P38 MAPK signaling pathway while regulating mitochondria-NLRP3 inflammasome-microglia. Study design and methods: This work utilized triple transgenic mice (3 x Tg-AD) as AD models and A beta(25-35) was used to induce BV2 cells to build an in vitro AD model. Behavioristics, pathology and related inflammatory factors were examined. Molecular mechanisms are investigated by western-blot, immunofluorescence staining, CETSA, molecular docking, network pharmacology. Results: According to our findings, Myr could remarkably improve memory loss, spatial learning ability, A beta plaque deposition, neuronal and synaptic damage in 3 x Tg-AD mice through specifically inhibiting P38 MAPK pathway activation while restraining microglial hyperactivation. Furthermore, Myr promoted the transformation of microglial phenotype, restored the mitochondrial fission-fusion balance, facilitated mitochondrial biogenesis, and restrained NLRP3 inflammasome activation and neuroinflammation. For the in-vitro experiments, P38 agonist dehydrocorydaline (DHC) was utilized to confirm the key regulatory role of P38 MAPK signaling pathway on the mitochondria-NLRP3 inflammasome-microglia channel. Conclusions: Our results revealed the therapeutic efficacy of Myr in experimental AD, and implied that the associated mechanism is possibly associated with inhibiting tmitochondrial dysfunction, activating NLRP3 inflammasome, and neuroinflammation which was mediated by P38 MAPK pathway. Myr is the drug candidate in AD therapy via targeting P38 MAPK pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that several of the panels showing the results from cell migration and invasion assay experiments in Fig. 2 on p. 628 contained sections of data that were overlapping with other panels within the same figure. Given the issue of the overlapping sections of data, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal on account of an overall lack of confidence in the presented results. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 8: 626‑630, 2013; DOI: 10.3892/mmr.2013.1501].

Background: VISTA and HHLA2 are two recently identified members of the B7 homologue family of immune-regulatory molecules. But the expression patterns and clinical significance of VISTA and HHLA2 in lung adenocarcinoma (LUAD) remain largely unknown. Methods: Immunohistochemistry was performed to examine the expression of VISTA, HHLA2, PD-L1 and CD8+ tumor-infiltrating lymphocytes in 74 cases of LUAD. The expression of VISTA, HHLA2, PD-L1, CD68 and CD8 proteins was detected by multiplex immunofluorescence staining in the LUAD tissues. Results: High expression of VISTA and HHLA2 was observed in LUAD compared with noncancerous tissues. High VISTA expression in immune cells predicted a high mortality rate and worse survival. Conclusion: VISTA and HHLA2 are potential immunotherapeutic targets that possess different prognostic significance in LUAD.