Osteoarthritis is a multifactorial condition marked by the gradual deterioration of joint cartilage, synovial inflammation, alterations in the subchondral bone and changes in the surrounding soft tissues. Clinical assessments and patient-reported outcome measures can identify pathological tissue alterations in osteoarthritis, in conjunction with radiographic evaluation of osteophytes, bone sclerosis, and joint space reduction. Although available treatments can help manage symptoms, early identification of prognostic factors for osteoarthritis progression is crucial for personalizing interventions and improving long-term outcomes. Therefore, it is essential to identify the key factors that can influence the disease's progression, including biological, mechanical, and clinical aspects. This review synthesizes current findings on the prognostic and diagnostic value of various biomarkers (systemic, intrinsic) and prognostic factors (biochemical, genetic, epigenetic) in knee and hip osteoarthritis. We also discuss the role of machine learning tools in identifying new biomarkers associated with osteoarthritis development and progression, paving the way for translation to clinical studies. In addition, we discuss recent studies aimed at identifying potential biomarkers and molecules that could serve as therapeutic strategies for osteoarthritis treatment.

Leukemia, a group of malignant blood disorders, arises from the uncontrolled proliferation of abnormal white blood cells. Genetic mutations play a critical role in the initiation and progression of leukemia. This review aims to provide an overview of the genetic landscape of leukemia, focusing on the most common genetic alterations and their clinical implications. A literature search was conducted to identify relevant studies on genetic mutations in leukemia. The identified studies were critically appraised to assess their methodological quality. The present review highlights the key genetic alterations associated with different types of leukemia, including chromosomal translocations, point mutations, and gene copy number variations. These genetic abnormalities can impact disease prognosis, treatment response, and overall patient survival. A comprehensive understanding of the genetic basis of leukemia is essential for accurate diagnosis, prognostication, and the development of targeted therapies. Future research should focus on identifying novel genetic markers, elucidating the underlying mechanisms of leukemogenesis, and developing innovative therapeutic strategies.

Background: Whether seizure presentation in patients afflicted with primary brain tumors (PBT) is associated with clinical prognosis remains an open question. We explore this association using the Nationwide Readmission Database (NRD).

Methods: A systematic literature review was conducted to summarize prior studies focusing on the association between the presence of seizure and outcomes of PBT/brain metastases (BM). The statistical power of the study was defined as a function of the effect size. We identified 50,380 and 32,789 PBT and BM patients in the NRD (2010–2018), respectively. Multivariable logistic regression models were utilized to assess the risk of mortality and the related factors.

Results: In a multivariable model accounting for known survival pertinent variables (age, gender, insurance status, income, hospital length of stay, discharge disposition, hospital features), the adjusted odds ratio (aOR) of death for PBT patients who presented with seizures and underwent craniotomy was 0.67 [95% Confidence Interval (CI): 0.52–0.86, p = 0.002] relative to those presented without seizures. The aOR of death for PBT patients who presented with seizures and underwent biopsy was 0.55 (95% CI: 0.30–1.00, p = 0.048) relative to those without seizures. This association was not observed for BM patients; the aOR of death for BMs who presented with seizures was 0.91 (p = 0.483) and 0.32 (p = 0.090) relative to those presented without seizures for craniotomy and biopsy patients, respectively. A comprehensive review of the literature showed that the predominance of the available studies supported the reported association.

Conclusions: We report an association between seizure at presentation and decreased mortality risk for PBT patients. The association was robust in both patients who underwent craniotomy as well as stereotactic needle biopsy but was not observed in BM patients.

Background: Cardiovascular diseases, including coronary artery disease (CAD), represent one of the leading causes of death worldwide. Individuals with type 2 diabetes mellitus (T2DM) are susceptible to more severe forms of CAD. Given the strong genetic basis underlying the pathogenesis of T2DM and CAD, this study aimed to investigate the potential significance of the following genetic variants in the pathogenesis of CAD with and without T2DM comorbidity: hepatocyte nuclear factor-1 alpha (HNF1A) [p.I27L] rs1169288, glutathione S-transferase Pi 1 (GSTP1) rs1695 (A>G; Ile→Val), transcription factor 7-like 2 (TCF7L2) rs7903146 (C>T), and long non-coding RNA H19 (LncRNA H19) rs217727 (C>T).

Methods: Three hundred subjects were enrolled in this study, containing 200 cases of CAD (100 non-diabetic and 100 diabetic) and 100 healthy individuals as controls. The genotyping studies were conducted using amplification-refractory mutation system polymerase chain reaction (ARMS-PCR).

Results: Demographic and clinical characteristics associated with the two CAD groups demonstrated significant differences. Additionally, a significant difference in genotype frequencies of the GSTP1 (rs1695 A>G) gene polymorphism was detected between CAD patients and healthy controls, with the GG genotype being more common in CAD patients (18% in non-diabetic and 20% in diabetic) than in the healthy controls (3%) (p < 0.0001 and p = 0.00003). Those with the GG genotype had a notably higher risk of developing CAD, regardless of T2DM comorbidity. The LncRNA H19 (rs217727 C>T) gene polymorphism displayed significant differences in genotype frequencies between healthy controls and non-diabetic CAD patients, but not in diabetic CAD patients. The TT genotype was much more common in non-diabetic CAD patients (20%) compared to healthy controls (6%, p = 0.0006), with nondiabetic patients also having a higher frequency of the T allele (0.42 vs. 0.23 in controls). Similarly, the TCF7L2 (rs7903146 C>T) gene polymorphism displayed significant differences in genotype frequencies between healthy controls and non-diabetic CAD patients, instead of diabetic CAD patients. The CT heterozygous genotype was more common in non-diabetic CAD patients (63%) than in healthy controls (35%, p = 0.0001). The HNF1A (rs1169288 G>T) gene polymorphism showed significant differences in genotype frequencies between healthy controls and diabetic CAD patients, but not between non-diabetic CAD patients. The TT genotype was notably overrepresented in diabetic CAD patients (8%) than in healthy controls (1%, p = 0.04), and diabetic patients also had a higher frequency of the T allele (0.38 vs. 0.33 in controls).

Conclusion: The data from the current study have identified certain genetic variants of interest in the given population as risk markers of CAD with and without T2DM comorbidity.

Background: Chlorogenic acid (CGA) exerts immunomodulatory effects by regulating the proportion of regulatory T cells (Tregs), and T-cell dysregulation is a known feature of post-traumatic osteomyelitis (PTO). This study explored the mechanism of CGA in the treatment of PTO from the perspective of T-cell immunity.

Methods: Lymphocytes isolated from rat spleens were stimulated with interleukin (IL)-2. A PTO model was established by injecting Staphylococcus aureus into the tibial marrow cavity of New Zealand white rabbits. PTO rabbits were treated with either CGA by gavage or lentiviral IL-2 injection. The Treg proportion was evaluated by flow cytometry. The expression of forkhead box protein 3 (Foxp3), cytotoxic T lymphocyte antigen-4 (Ctla-4), and IL-2 was quantified by quantitative real-time polymerase chain reaction. The concentrations of tumor necrosis factor-α (TNF-α), IL-10, and IL-2 were measured using enzyme-linked immunosorbent assays. Micro-computed tomography and hematoxylin and eosin staining were performed to characterize bone destruction. The proliferation of CD4⁺ T/CD8⁺ T cells was evaluated by flow cytometry.

Results: IL-2 stimulation elevated the proportion of Tregs in rat splenic lymphocytes, upregulated Foxp3, Ctla-4, and IL-10 expression, and decreased TNF-α expression (p < 0.05). PTO rabbits exhibited significant bone destruction and inflammatory cell infiltration in bone tissue. In the peripheral blood of PTO rabbits, the Treg proportion was elevated, with increased expressions of Foxp3, Ctla-4, IL-10, and IL-2, reduced TNF-α expression, and increased proliferation of CD4⁺ T/CD8⁺ T cells. These changes were significantly reversed by CGA administration (p < 0.001). However, the reversal effects of CGA were offset by exogenous IL-2 (p < 0.001).

Conclusion: CGA alleviates PTO by inhibiting IL-2-mediated upregulation of Tregs.

Background: Ageing is associated with a significant decline in olfactory function, though the underlying mechanisms remain unclear. Angiotensinogen (AGT) participates in multiple cellular processes, including inflammation, oxidative stress (OS), and magnesium (Mg²⁺) homeostasis. In this study, we investigated how decreased AGT expression in olfactory epithelial cells affects Mg²⁺ uptake, inflammation, oxidative stress, and mitochondrial apoptosis, ultimately contributing to olfactory dysfunction.

Methods: Rapidly ageing male senescence-accelerated mouse prone 6 (SAMP6) mice and age-matched normal senescence accelerated mouse resistant 1 (SAMR1) control mice were used to evaluate olfactory function via the buried food test. Blood and olfactory epithelium tissues were collected for biochemical analyses. Mouse olfactory epithelial (MOE) cells were cultured, and AGT expression was knocked down, with or without MgSO₄ supplementation. Mitochondrial membrane potential (Δψm) was assessed using JC-1 staining, and cell viability was measured via Cell Counting Kit-8 (CCK-8) assay.

Results: SAMP6 mice exhibited impaired olfactory function, with significant structural damage to the olfactory epithelium and reduced expression of olfactory marker protein (OMP, p < 0.05). Elevated expression of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), reactive oxygen species (ROS), Bcl-2-associated X protein (Bax), caspase-3, and caspase-9 was observed in blood and olfactory epithelium tissues, while levels of AGT, Angiotensin II (Ang II), Mg²⁺, and the Mg²⁺ transporter mitochondrial RNA splicing 2 protein (MRS2) and transient receptor potential cation channel subfamily M member 6 (TRPM6) were significantly decreased (p < 0.05). In vitro, AGT knockdown reduced viability and Δψm in MOE cells (p < 0.05), elevated IL-1β, TNF-α and ROS (p < 0.05), and suppressed the expression of AGT, Ang II, MRS2, and TRPM6 (p < 0.05). Notably, MgSO₄ administration partially reversed the effects of AGT knockdown on MOE cells (p < 0.05).

Conclusion: Reduced AGT expression in olfactory epithelial cells impairs Mg²⁺ uptake, leading to inflammation, oxidative stress, and mitochondrial apoptosis, ultimately contributing to age-related olfactory dysfunction. Our findings suggest that targeting AGT or Mg²⁺ homeostasis may offer promising therapeutic strategies for age-related olfactory disorders.

Background: Corneal chemical burns are a common form of ocular injury that can result in severe visual impairment and complications. In recent years, studies have shown that unilateral ocular diseases can induce changes in the contralateral eye; however, the impact of unilateral chemical injury on the contralateral eye remains unclear. This study aims to evaluate the contralateral ocular surface alterations in patients and experimental mice model with unilateral chemical injury.

Methods: 29 patients with single-eye chemical injuries and 28 normal volunteers as controls were included. Contralateral unaffected eyes were studied in the chemical injury group, while we picked one eye at random in the control group. All subjects completed the ocular surface disease index (OSDI) questionnaire and underwent a routine ophthalmic examination, including tear film break-up time (BUT), Schirmer I test (SIT), fluorescein staining and corneal sensitivity. Tear film height and bulbar redness were assessed using the Oculus Keratograph® (Wetzlar, Germany). In vivo confocal microscopy (IVCM) was employed to evaluate corneal nerve characteristics, Langerhans cell (LC) density, and their correlation with post-injury time. Additionally, an alkali ocular burn model was established in Bagg Albino Laboratory-bred strain (BALB/c) mice to observe corneal fluorescein staining, β-tubulin immunohistochemistry of the corneal nerve, and hematoxylin and eosin (H&E) staining. Furthermore, tear fluid from mice was collected for cytokine liquid chip analysis to assess the ocular surface inflammatory status.

Results: Compared to controls, the contralateral unaffected eyes of patients with unilateral chemical injury showed significantly higher OSDI scores and bulbar redness scores, along with significantly lower SIT and tear film height values (p < 0.05). In the chemical injury group, corneal nerves exhibited increased branching, severe tortuosity, along with higher sensitivity. Post-injury time was inversely correlated with corneal nerve branch density (p = 0.02) and nerve tortuosity (p = 0.038). The clinically unaffected eyes exhibited significantly higher LC density (p < 0.0001) in center cornea compared to the control group. In the experimental mouse model, the contralateral eye exhibited epithelial damage, characterized by increased fluorescein staining, corneal nerves tortuosity, and altered nerve direction. H&E staining revealed stromal thinning and widened interstitial spaces between collagen fibers. Additionally, tear fluid analysis of uninjured eyes indicated altered expression of fifteen inflammatory factors, with sustained upregulation of monocyte chemoattractant protein (MCP-1) after chemical injury.

Conclusion: In both clinical and animal experiments, we observed that unilateral ocular chemical injury can induce functional alterations in the contralateral ocular surface. The inflammatory response triggered by chemical injury is not confined to the injured eye. It is necessary for a comprehensive evaluation of the contralateral eye in clinical practice.

Objective: Pancreatic cancer (PC) is a type of highly malignant tumor associated with poor prognosis, whose progression is driven by hypoxia in the tumor microenvironment. This study aims to explore the effects of hypoxia-induced upregulation of acetyl-CoA synthetase 2 (ACSS2) on the proliferation and stemness of PC cells and its potential molecular mechanism, so as to provide new targets and therapy strategies for the PC.

Materials and Methods: PC cells (PANC-1) were cultured under separate conditions: hypoxic and normoxic. Cell models of ACSS2 overexpression, ACSS2 knockdown and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) knockdown were constructed using transfection technique. Cell counting kit 8 (CCK-8) and clonal formation assay were used to assess cell viability, and cell stemness was analyzed by means of sphere-formation assay and detection of stem-related markers. A mouse tumor model was established by axilla injection of tumor cells, and tumor growth was evaluated by measuring the volume and weight of the isolated tumors. Relative mRNA and protein levels were analyzed by quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry.

Results: Hypoxic condition upregulated the expression of ACSS2 in PC cells. CCK-8 and clonal formation assays showed that upregulation of ACSS2 promoted cell proliferation (p < 0.001), while knockdown of ACSS2 inhibited cell proliferation (p < 0.001). Sphere formation assay and stemness marker detection showed that ACSS2 upregulation could maintain cell stemness (p < 0.001), while knockdown could inhibit it (p < 0.01). Through mechanistic studies, we found that ACSS2 activated phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway through HMGCS1. Interference with HMGCS1 inhibited pathway activation caused by ACSS2 upregulation and hindered cell proliferation and stemness. In vivo experiments further demonstrated that ACSS2 accelerated PC xenograft tumor growth and promoted tumor stemness.

Conclusion: Hypoxia induces upregulation of ACSS2 and activates PI3K/AKT/mTOR pathway through HMGCS1, thereby enhancing the proliferation and stemness of PC cells. This finding offers a novel perspective for understanding the development mechanism of PC and highlights a potential molecular target for developing targeted therapeutic strategies.

Objective: This study aimed to elucidate the protective effects of quercetin (Que) on the gastric mucosa in a rat model of chronic atrophic gastritis (CAG), with emphasis on the regulation of the transforming growth factor-beta1 (TGF-β1)/Smads signaling pathway.

Methods: Wistar rats were randomly divided into five groups: control, model, low-dose Que (Que-L), and high-dose Que (Que-H). After 30 days of oral gavage, the rats were euthanized for further analysis. Histopathological changes, gastric function (pH, secretion volume, and pepsin activity), and serum levels of gastrin-17 (G-17), interleukin-17 (IL-17), proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and growth hormone (GH) were evaluated. The expression levels of PCNA, VEGF, TGF-β1, Smad4, and Smad7 were determined by quantitative real-time PCR (qRT-PCR) and Western blot. Gastric epithelial cells-1 (GES-1) cells were infected with Helicobacter pylori (H. pylori) and treated with Que and the TGF-β1/Smad pathway activator SRI-011381. Cell viability, morphological damage, and TGF-β1/Smads pathway expression were subsequently assessed.

Results: Rats in the model group exhibited significantly increased gastric juice pH, decreased total gastric secretion volume and pepsin activity, elevated serum levels of PCNA, VEGF, and EGF, and reduced levels of GH and G-17 (p < 0.05). In gastric tissues, PCNA, VEGF, Smad4, and TGF-β1 were upregulated, while Smad7 was downregulated (p < 0.05). Que treatment improved gastric function, normalized serum biomarkers, and decreased the expression of PCNA, VEGF, Smad4, and TGF-β1, while upregulating Smad7 (p < 0.05). In H. pylori-infected GES-1 cells, Que suppressed PCNA and VEGF expression, enhanced cell viability, and improved nuclear morphology (p < 0.05). It also downregulated TGF-β1 and Smad4 while restoring Smad7 expression. Pretreatment with SRI-011381 attenuated the protective effects of Que (p < 0.05).

Conclusion: Que alleviates gastric inflammation, improves gastric secretory function, and modulates key molecular markers (PCNA, EGF, VEGF, G-17, and GH), thereby protecting against gastric mucosal injury in CAG rats. These effects are likely mediated through inhibition of the TGF-β1/Smads signaling pathway.

Background: To analyze the efficacy of the improved sampling method in enhancing the accuracy of Human Epidermal Growth Factor Receptor 2 (HER2) detection within gastric cancer surgical specimens, in order to decrease the false negative rate of HER2 detection results.

Methods: In this study, the participants were gastric cancer patients recruited from the Shandong Cancer Hospital Affiliated with Shandong First Medical University. Between December 2018 to August 2020, 310 surgical specimens of gastric cancer were procured and processed using traditional sampling methods. Biopsy specimens (n = 235), and surgical specimens (n = 400) indicated for processing by improved sampling methods, were obtained during the period from September 2020 to July 2021. Clinical data including sex, age, stage, degree of differentiation, tumor site, operation duration and blood loss was collected. Sex, operation duration and blood loss among three groups were compared by One-Way analysis of variance (ANOVA), and sex, stage, degree of differentiation and tumor site comparisons were performed by Chi-squared test (χ²). HER2 detection was carried out for all specimens by means of immunohistochemical (IHC) assay. The results of HER2 detection among three groups were compared by Chi-squared test (χ²) using SPSS software.

Results: There was no significant correlation between HER2 expression and pathological stage (p = 0.468). HER2 expression was related to tumor differentiation and tumor site: the HER2 expression in moderately differentiated tumors was higher than that in poorly differentiated tumors (p < 0.001); and it was significantly higher in gastric fundus than that in the gastric body and antrum (p = 0.031). The positive expression of HER2 in gastric cancer was 59.3% (0), 20.0% (1+), 13.4% (2+) and 7.3% (3+). Among them, a 2+ HER2 expression rate of 11.3%, 11.1%, and 16.5% were detected in specimens processed by the traditional sampling method, biopsy method, and tissues processed by improved sampling method, respectively. Meanwhile, a 3+ HER2 expression rate was found to be 4.8%, 8.1%, and 8.8%, respectively, for the specimens in the same order. Evidently, 1+ HER2 expression rate in specimens obtained by the improved sampling method and biopsy method was higher than in those by traditional sampling method (p < 0.001 and p = 0.007, respectively).

Conclusions: The improved sampling method significantly improves the positive HER2 expression rate (1+) in gastric cancer specimens, thereby reducing false-negative HER2 detection rates by immunohistochemistry. This method warrants further clinical implementation, particularly in resource-limited settings.

Background: Premature ovarian insufficiency (POI) is characterized by a reduction in primary follicle count along with abnormal follicle development. This study aims to explore the impact of combined oral contraceptives (COCs) on the apoptosis of ovarian granulosa cells, which are instrumental for follicular development, in POI and the underlying mechanisms, to provide theoretical guidance for the treatment of POI.

Methods: A rat model of POI was established using tripterygium glycoside tablets. After treatment with COCs, the therapeutic effect of the animals was verified by means of hematoxylin-eosin staining, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Flow cytometry, cell counting kit-8 (CCK-8), quantitative polymerase chain reaction, and Western blotting were utilized to investigate the impact of COCs on granulosa cell apoptosis, as well as the function of the interleukin (IL)-11/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Further experiments were also conducted to verify whether COCs could inhibit granulosa cell apoptosis through this pathway.

Results: COCs treatment was effective in improving ovarian granulosa cell status, reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and increasing estradiol levels in the POI rats (p < 0.01). IL-11 silencing promoted apoptosis in POI granulosa cells by inhibiting the PI3K/AKT pathway. COCs treatment partially reversed these effects by upregulating IL-11 expression and restoring PI3K/AKT pathway activity. This resulted in increased levels of B-cell lymphoma 2 (Bcl-2) (p < 0.05) and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) (p < 0.01), while suppressing the expression of Bax and cleaved-cysteine-aspartic acid protease 3 (cleaved-caspase 3) (p < 0.001).

Conclusion: Our findings demonstrated that COCs protect ovarian granulosa cells from apoptosis in rats with POI, an effect mediated through the IL-11/PI3K/AKT signaling cascade.

Background: Asthma is a common respiratory system disease characterized by airway inflammation and airway remodeling. Amygdalin, an active component of the traditional Chinese medicine Bitter Almonds, has been shown to inhibit liver fibrosis via the inactivation of the transforming growth factor-beta 1 (TGF-β1)/Smads pathway. This study aims to investigate the effects of Amygdalin on airway inflammation and remodeling in asthma, as well as its regulatory mechanisms.

Methods: An asthma mouse model was constructed using ovalbumin (OVA) induction. Mouse bronchoalveolar lavage fluid (BALF) and lung tissue were harvested for in vivo experiments, and airway smooth muscle cells (ASMCs) were isolated from BALB/c mice for in vitro experiments. The mechanism of Amygdalin and the TGF-β1/Smads signaling pathway in the mouse model was analyzed pathologically and molecularly using hematoxylin-eosin (HE) staining, Masson trichrome staining, Western blot, and enzyme-linked immunosorbent assay (ELISA).

Results: Amygdalin ameliorated the pathological abnormalities of lung tissues in the OVA-induced mouse model, reducing inflammation by downregulating OVA-specific immunoglobulin E (IgE) and inflammatory factors interleukin (IL)-4, IL-5, and IL-13 (p < 0.001). It also reduced lung tissue fibrosis (p < 0.01). Additionally, Amygdalin inhibited the levels of TGF-β1, p-Smad2, and p-Smad3 proteins (p < 0.05), and downregulated the fibrosis markers alpha-smooth muscle actin (α-SMA), Collagen I, and Collagen III expression in the OVA-induced asthma mouse model (p < 0.01).

Conclusion: Amygdalin can regulate the TGF-β1/Smads signaling pathway and alleviate airway inflammation and remodeling in an asthma model in mice.

Background: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is a severe form of pancreatitis, rapidly progressing to multiorgan failure. Growth arrest and DNA damage-inducible beta (GADD45B) play a crucial role in stress responses; however, its precise role in HTG-AP pathogenesis remains unknown. Therefore, this study aimed to elucidate the role of GADD45B in HTG-AP using both in vitro cellular and in vivo animal models.

Methods: AR42J cells were transfected with GADD45B si-RNA or overexpressed plasmids and induced with palmitic acid (PA) and caerulein (Cae) to establish an HTG-AP cellular model. The HTG-AP animal model was successfully developed by treating mice with P-407 and Cae, alongside adeno-associated virus (AAV)-shRNA interference. The transfection efficiency was assessed using quantitative PCR (qPCR) and Western blot analyses. Furthermore, cell viability was evaluated using the Cell Counting Kit-8 (CCK-8) assay, and cell death rate, inflammation levels, and pyroptosis were examined using Hoechst 33342/propidium iodide (PI) staining, enzyme-linked immunosorbent assay (ELISA), and transmission electron microscope (TEM). Moreover, protein expression levels of the pyroptotic pathway, nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain containing 3/Cysteine-dependent aspartate-specific protease 1/Gasdermin D (NLRP3/Caspase-1/GSDMD), were evaluated using Western blot analysis.

Results: The Co-IP assay confirmed the interaction between GADD45B and NLR family pyrin domain containing 3 (NLRP3). In the AR42J cell model of HTG-AP, GADD45B interference promoted cell viability, attenuated cell death, pro-inflammation, pyroptotic cytokines interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, IL-18, amylase, and intracellular vesicle counts (p < 0.05). Furthermore, AAV-shGADD45B treatment improved pancreatic injury, cell death, and pyroptosis in HTG-AP model mice (p < 0.05). Moreover, GADD45B knockdown suppressed the pyroptosis-related pathway NLRP3/Caspase-1/GSDMD protein levels (p < 0.05). However, GADD45B overexpression exhibited opposite effects, which was reserved by NLRP3 inhibitor MCC950 (p < 0.05).

Conclusions: This study revealed that GADD45B downregulation reduces pyroptosis by suppressing the NLRP3/Caspase-1/GSDMD axis in HTG-AP, underscoring GADD45B as a promising therapeutic target and enhancing its clinical application.

Background: Ovarian cancer (OC) is one of the most lethal forms of gynecological malignancies. Previous studies indicate that S100 calcium-binding protein A8 (S100A8) regulation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway has been implicated in the development and progression of a variety of cancers, but its effects and mechanisms in OC cells remain unclear. This study aims to explore the effect of S100A8 on autophagy and apoptosis in OC cells and the regulatory effects of the PI3K/Akt signaling pathway.

Methods: Viability of OC cells was assessed by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell migration was determined using the Transwell assay. The effect of S100A8 on autophagy in OC cells was assessed using immunofluorescence and transmission electron microscopy. Flow cytometry analysis was conducted to assess apoptosis. To study the expression of genes associated with cell viability, migration, autophagy, apoptosis, and the PI3K/Akt signaling pathway, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were performed.

Results: High concentrations of S100A8 protein significantly inhibited the activity of OC cells, with the most pronounced effect observed at 72 hours (p < 0.05). S100A8 protein inhibited the proliferation of OC cells and decreased the expression level of migration-driving factors (p < 0.05). S100A8 protein promoted apoptosis and inhibited the protein levels of Beclin 1 and microtubule-associated protein 1 light chain 3-II (LC3-II) in OC cells (p < 0.05). However, the PI3K/Akt activator blocked the inhibitory effects of S100A8 on OC cell activity, autophagy, and migration, and hindered it from promoting apoptosis.

Conclusions: With its ability to inhibit proliferation, migration, and autophagy, and promote apoptosis in OC cells by inhibiting the PI3K/Akt pathway, S100A8 holds promise as a potential target for the prevention and treatment of OC, providing an effective therapeutic strategy for the clinic.

Aim: Primary sarcomatoid carcinoma (PSC) of the lung is a rare malignant neoplasm characterized by the presence of both carcinomatous and sarcomatoid components, typically presenting as a solitary pulmonary mass. Imaging examination serves as a critical tool for the detection and evaluation of pulmonary lesions, the definitive diagnosis of PSC still relies on histopathological examination and immunohistochemical staining results. This study presents a pathologically confirmed case of PSC of the lung with a retrospective analysis of the clinical features and chest computed tomography (CT) imaging findings. The purpose is to improve the diagnostic accuracy of this disease.

Case Presentation: A 67-year-old Chinese male was admitted to the First People's Hospital of Tong Xiang City with a one-week history of cough and expectoration. A plain and contrast-enhanced chest CT scan revealed a large mass in the upper lobe of the right lung, adjacent to the interlobar fissure and parietal pleura. Upon enhancement, the mass demonstrated irregular mild-to-moderate enhancement on the side near the pleura, with no significant enhancement in the central region or near the hilum. A pseudocapsule was observed surrounding the lesion. The patient subsequently underwent resection of the right upper lobe mass. Hematoxylin-eosin staining of the pathological specimen revealed spindle-shaped tumor cells that had invaded the parietal pleura. Immunohistochemical analysis showed positivity for vimentin and cytokeratin, as well as partial positivity for epithelial membrane antigen. Based on these immunohistochemical findings, the tumor was diagnosed as pulmonary sarcomatoid carcinoma (spindle cell type). Approximately 10 months postoperatively, the patient was readmitted due to chest pain and dyspnea lasting four days. The chest CT scan indicated tumor recurrence. The patient was managed conservatively for two months, achieving stable condition before discharge. Two months after discharge, the patient succumbed to complications of concurrent pulmonary infection and cardiopulmonary failure.

Results: Analyzing the pathological findings and CT manifestations in a patient with pulmonary PSC; immunohistochemical staining results can to some extent provide insights into the patient's prognosis.

Conclusions: Owing to the rarity, high-degree malignancy and poor prognosis of PSC, potential cases should be comprehensively evaluated based on imaging, laboratory and pathological results. Long-term regular follow-up is required to rule out the metastasis or recurrence of postoperative pleural metastasis.