Hip osteoarthritis (HOA) is the most common hip joint disorder, accounting for approximately 27.9% of all cases of osteoarthritis (OA), often leading to total hip replacement (THR). In the last decades, femoroacetabular impingement (FAI) has been addressed as a significant etiological factor in the development of early-onset HOA, especially in young adults with non-dysplastic hips. FAI has been found to cause damage to all joint tissues, cartilage, labrum, and subchondral bone, thus underlining the importance of an early diagnosis and intervention to prevent progression to end-stage disease. This review aims to provide a comprehensive overview of the biochemical, morphological, and cellular alterations occurring in hip joint tissues in the presence of FAI. Understanding the early pathological changes is of crucial importance as they often precede radiographic signs of disease and may serve as valuable biomarkers for early detection and management of FAI and peri-arthritic conditions to delay or prevent the need for THR in younger populations.

The age-standardized point prevalence of global osteoarthritis (OA) has increased, and OA will not only lead to disability in patients but also to a greater psychological burden. In recent years, the focus of scientists on treating OA has turned to disease prevention and treatment of early OA. Previous studies have proved that WuFu Decoction (WFD) could protect chondrocytes, and the Chinese herbs in this prescription have shown anti-inflammatory effects. In this study, we built the OA rat model by the modified Hulth method, conducted research with WFD, and set D-Glucosamine sulfate as the positive control. It is proven that WFD improved the micromorphology and tissue damage of the knee joint, decreased the score of the Mankin and OARSI system, and inhibited the IL-1β, TNF-α, MMP-13, and CTX-1 levels in serum. Additionally, WFD treatment inhibited p-ERK1/2 levels and raised the mRNA and protein levels of TGF-β1, p-Smad2, p-Smad3, type II collagen (the gene is COL2A1), ALP, TRACP, and BMP7. Furthermore, TGF-β1 inhibitor (Decorin) reversed the improvement effect of WFD on OA, but ERK1/2 inhibitor (PD98059) promoted this improvement effect. Silencing TGFβR2 can reverse the protective effect of WFD on primary chondrocytes. It is suggested that WFD can improve OA and chondrocytes by regulating the TGF-β1/Smad and ERK1/2 pathways. This study also identified active ingredients, such as Fumaric acid, Glycyrrhizic acid, Albiflorin, and Isoliquiritigenin. It provides a basis for the clinical application of WFD and for the promotion and development of TCM.

Periostin is involved in airway remodeling, salivary tumors, and various otolaryngological diseases. D-β-aspartic acid is the major isomer of D-aspartic acid found in the tissues of elderly individuals. In this study, we investigated the expression and role of D-β-aspartic acid and periostin in the formation of benign parotid tumors. The data of 36 patients (16 male and 20 female) who underwent parotid tumor resection between April 2017 and March 2022 and were clinically and pathologically diagnosed as having benign parotid tumors were included in this study. The mean age of the patients was 59.2 (range 26-82) years. Tumors were histologically classified as pleomorphic adenomas, Warthin's tumors, basal cell adenomas, oncocytomas, and myoepitheliomas. Increased D-β-aspartic acid expression was observed in the epithelium and stroma of benign parotid tumors. In the epithelium, D-β-aspartic acid was found in 35 of 38 samples (92.1%). In the stroma, it was found in 19 of 38 samples (50.0%). In the stroma of benign parotid tumors, increased expression of periostin was found in 32 of 38 samples (84.2%). Four periostin expression patterns were observed in benign parotid tumors: negative, superficial, infiltrative, and diffuse. Statistically significant differences were found between the expression pattern of D-β-aspartic acid in the stroma and the histological classification of benign parotid gland tumors. In addition, a statistically significant difference was found between the expression patterns of D-β-aspartic acid and periostin in the stroma. Our results suggest that D-β-aspartic acid and periostin may be involved in the pathogenesis of benign parotid gland tumors.

Although C6orf15 is highly expressed in certain human cancers, its expression pattern in papillary tumors remains unclear. In this study, we investigated C6orf15 expression in papillary tumors and assessed its potential as a diagnostic biomarker for histopathological evaluation and fine-needle aspiration cytology (FNAC). We collected a total of 87 formalin-fixed and paraffin-embedded (FFPE) thyroid tissue specimens that included: 10 cases with Hashimoto's thyroiditis (HT), 11 with follicular adenomas (FAs), two with non-invasive follicular thyroid neoplasms with papillary-like nuclear feature (NIFTP), six with follicular thyroid carcinomas (FTCs), three with invasive encapsulated follicular variant of papillary thyroid carcinomas (IEFVPTCs), three with medullary thyroid carcinomas (MTCs), and 52 with papillary thyroid carcinomas (PTCs). Additionally, 33 FNAC samples from thyroid nodules were analyzed, comprising three samples of FA, five atypia of undetermined significance (AUS), and 25 cases of PTC. Immunohistochemical (IHC) staining was performed to assess C6orf15 expression in thyroid tumor tissues and FNAC samples. We conducted BRAF V600E mutation analysis via Sanger sequencing and IHC and discerned that C6orf15 expression was absent in normal follicular epithelial cells, FA, NIFTP, TFC, and MTC. The positivity rates for C6orf15 in FFPE samples were as follows: 66.7% for IEFVPTC, 86.5% for PTC, and 60.0% for AUS. In FNAC samples, the positivity rate was 80.0% for PTC. A significant positive correlation was observed between C6orf15 expression and the BRAF V600E mutation in PTC tissues (p<0.001), but no such association was found in FNAC samples (p=0.230). C6orf15 exhibited high expression levels in the majority of IEFVPTC (66.7%), PTC tissues (86.5%), and FNAC samples (80.0%). These findings suggest that C6orf15 constitutes a promising diagnostic biomarker for the classic variant of PTC and is applicable to histopathological assessment and FNAC-based diagnosis.

Synovial pathology impacts joint disease progression and clinical outcome. The goal of this study was to modify Krenn synovitis score for more accurate and comprehensive evaluation of common orthopaedic joint conditions. A total of 31 synovial samples were collected during foot and ankle surgery. Synovial sections were stained with hematoxylin and eosin, and picrosirius red. Immunohistochemistry for CD3 and α-smooth muscle actin (α-SMA) was performed for inflammatory infiltration and fibroblast activation. Synovitis was evaluated with Krenn synovitis score and a modified Krenn synovitis score (MKSS), where the original subcategories of inflammatory infiltration and stromal cellularity were replaced with the density of CD3+T cells and collagen intensity, respectively. Of 31 synovial samples, the average Krenn synovitis score was 1.5±1.3 and MKSS was 1.8±1.2 (p>0.05). The two scores were positively correlated in assessing synovial pathology (r=0.6; p<0.001). The dominant subcategory shifted from stromal cellularity (64%) in Krenn synovitis score to the density of CD3+T cells (80%) in MKSS. By MKSS classification, but not Krenn synovitis score, type III collagen intensity and the ratio of type III over type I collagen increased in the synovitis group. The density of α-SMA+cells did not correlate with the intensity of synovial collagen and was not different between synovitis and non-synovitis samples. While maintaining the concept and basic elements of the Krenn synovitis score, MKSS incorporated more accurate inflammatory infiltration and detailed fibrosis. It could provide a more comprehensive evaluation of synovial pathology in common orthopaedic joint conditions.

Aging induces alterations in bone microarchitecture, including bone function. This study aimed to identify histological changes in the components of cranial bones of the human skull and to investigate their relationship with aging. In this study, sixty-four fresh cranial remains were examined with an age range of 43-90 years, the crania being randomly selected to investigate the microstructure of the frontal, temporal, parietal, and occipital bones, which were stained using picrosirius red. Our results observed similar histological changes in the frontal, temporal, parietal, and occipital bones. Results of the histomorphological analyses demonstrated that there was an age-related gradual increase in the number of osteons. A distinct increase in the number of osteons in the cortical bone was found, particularly over 60 years. As age increased, the area of the circumferential lamellae adjacent to the periosteum also tended to diminish. A greater lamellar area was found in association with younger individuals, the area declining with age. In some samples from individuals older than 80 years, the outer circumferential lamellae were no longer visible. In addition, there was an association between cortical porosity and numbers, and the enlargement of porosity and age. The size of the pores in the cancellous bone tended to increase as well. This histomorphological study increases the comprehension regarding the relationship between the aging process and the structure of the human cranial bone in adults, and the results can be regarded as alternative data in the determination of age in humans.

Renal tumors encompass a diverse group of neoplasms with distinct morphological and molecular features. Recent research has highlighted the stimulator of interferon genes (STING) pathway as a key player in tumorigenesis, immune modulation, and autophagy across various renal tumor histotypes. This review explores the biological, diagnostic, prognostic, and therapeutic implications of STING in both epithelial and mesenchymal renal neoplasms. In clear cell renal cell carcinoma, STING expression correlates with aggressive histological features and poor clinical outcomes, suggesting a role in immune evasion and tumor progression. Similarly, in fumarate hydratase-deficient renal cell carcinoma, STING activation, driven by mitochondrial dysfunction and fumarate accumulation, aligns with PD-L1 expression and tumoral inflammatory infiltrate, supporting its potential function as a predictive biomarker of immunotherapy response. In renal perivascular epithelioid cell (PEC) proliferations, widespread STING expression is linked to autophagy regulation and mTOR pathway interaction, offering novel therapeutic insights. The dual role of STING in promoting or suppressing inflammation underscores the therapeutic potential of both agonists and antagonists of this pathway, depending on the specific tumor entity. Moreover, STING's interplay with interferons and cytokines, such as IL-6 and IFNγ, further supports its relevance in modulating immune responses and treatment efficacy. Despite current limitations, accumulating evidence places STING as a promising biomarker and therapeutic target in numerous renal tumors. Future studies are warranted to clarify its mechanistic roles and optimize its clinical application across renal tumor subtypes.

Yolkin is an egg yolk-derived protein with immunoregulatory properties. In this work, yolkin was evaluated as a protective agent in endotoxemic BALB/c mice. The mice were pretreated with yolkin either orally in drinking water or intraperitoneally (i.p.) before i.p. injection of E. coli lipopolysaccharide (LPS). Circulating blood leukocyte number, blood cell composition, serum levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and haptoglobin, as well as histological changes in the spleen and the liver, were examined. Yolkin differentially regulated the values of these parameters, depending on the administration protocol; however, the serum levels of TNF-α and IL-6 were generally decreased, and the level of haptoglobin, an acute-phase protein, was elevated. The pretreatment of mice with yolkin led to improved histological architecture in the investigated organs of endotoxemic mice, particularly in the liver, where yolkin diminished an increased level of vascular permeability and reversed a decreased number of Kupffer cells. These changes were independent of the route of yolkin administration. In conclusion, yolkin proved effective in the amelioration of pathogenic consequences of LPS administration and may be considered a potential protective measure for patients at risk of endotoxemia.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is a physiologically active form of vitamin D. Our study investigated the renoprotective functions of 1,25(OH)2D3 in diabetic nephropathy (DN) progression and its underlying mechanism targeting the ROS/TXNIP/NLRP3 inflammasome pathway. DN was induced in Wistar rats via high-fat diet (4 weeks) and streptozotocin injection (30 mg/kg, i.p.); hyperglycemic rats were randomized into DN and DN + 1,25(OH)2D3 (16 μg/kg, 12 weeks) groups. Rat mesangial HBZY-1 cells were maintained under normal glucose (5.5 mM), high glucose (25 mM), high glucose plus 1,25(OH)2D3 (1-50 nM), or high glucose plus N-acetylcysteine (NAC, 10 mM). Cell viability was assessed by the CCK-8 assay. Oxidative stress parameters (ROS via DCFH-DA fluorescence, MDA content, SOD activity) and pyroptosis markers (LDH release, PI/Hoechst 33342 nuclear staining) were quantified. Renal histopathology was performed using PAS and Masson trichrome staining. Biochemical analyses included serum creatinine, urea nitrogen, and 24-h urinary protein quantification. Molecular profiling encompassed ELISA (IL-1β, IL-6, TNF-α, IL-18, fibronectin, collagen IV), RT-qPCR (NOX2, NOX4, NLRP3, ASC), western blotting (TXNIP, NLRP3, ASC, caspase-1, IL-1β, IL-18, collagen IV, fibronectin, laminin), and TXNIP immunofluorescence. 1,25(OH)2D3 significantly attenuated high glucose-induced pathological alterations in HBZY-1 cells, including ROS overproduction, TXNIP upregulation, NLRP3 inflammasome activation, oxidative stress, inflammation, extracellular matrix (ECM) deposition, and pyroptotic cell death. Consistently, 1,25(OH)2D3 suppressed ROS/TXNIP/NLRP3/caspase-1 signaling, ameliorated renal dysfunction, and mitigated histopathological damage in DN rats. 1,25(OH)2D3 confers renoprotection in DN by inhibiting the ROS/TXNIP/NLRP3 inflammasome axis, thereby suppressing oxidative stress, inflammatory cytokine production, ECM accumulation, and pyroptotic cell death in glomerular mesangial cells and renal tissues.

Acute exposure to seizurogenic chemicals, such as organophosphates (OPs) or domoic acid (kainate analogue), can trigger status epilepticus (SE), marked by central (seizures) and, with OPs, peripheral effects due to irreversible inhibition of acetylcholinesterase (AChE). The initial seizurogenic activity in the brain initiates a cascade of molecular and cellular changes, known as epileptogenesis, the process by which epilepsy develops. Among the several signaling pathways involved in epileptogenesis, this review discusses the roles of the Src family of tyrosine kinases (SFK), especially Fyn kinase, and inducible nitric oxide synthase (iNOS) mediated mechanisms. Both signaling molecules are upregulated following initial seizures and persist for a long time, contributing to neuroinflammation, elevated levels of reactive oxygen and nitrogen species (ROS/RNS), and proinflammatory cytokines, as well as neurodegeneration and spontaneously recurring seizures. Epilepsy is a progressive disease associated with unprovoked seizures and cognitive decline. While the current standard of care can alleviate symptoms and reduce mortality, they do not address long-term neurological consequences. In this review, we discuss preclinical testing of two CNS-targeted drugs, iNOS and SFK inhibitors 1400W and Saracatinib (SAR; AZD0530), respectively, as potential disease-modifiers.