Tissue Changes Research Articles

TOXICOLOGICAL IMPACT OF DICLOFENAC SODIUM: HEMATOLOGICAL, BIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES IN MALE RATS

Background: Long-term administration of diclofenac sodium can lead to harmful effects on body tissues, causing cellular injuries that include changes in kidney function and contributing to the development of immune mechanisms against kidney tissues. This study aimed to evaluate the toxic effects of diclofenac sodium on hematological and biochemical parameters, as well as histopathological changes in the kidneys of experimental animals. Methods: Forty male Albino-Aster mice were divided into four groups: control and three groups administered diclofenac sodium orally at doses of 20.5, 45 and 56.25 mg/kg body weight for 20 days. Blood samples were collected for hematological and biochemical analyses and kidney tissues were examined histopathologically. Results: Diclofenac sodium administration caused a significant decrease in red blood cells, hemoglobin, packed cell volume, mean corpuscular volume and mean corpuscular hemoglobin concentration, as well as a significant increase in platelets and total white blood cells. Serum alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase were significantly elevated. Histopathological examination revealed congestion, inflammation, glomerular abnormalities, tubular necrosis and vascular changes in the kidney tissues, with the severity increasing with higher doses. Conclusion: Diclofenac sodium administration at different doses can cause significant alterations in hematological and biochemical parameters, as well as histopathological changes in the kidneys of male rats, indicating potential adverse effects on animal tissues. Caution is recommended in the clinical use of diclofenac sodium and the lowest effective dose and duration should be used to achieve the desired therapeutic effect.

MiR-142-3p Regulates Airway Inflammation Through PTEN/AKT in Children and Mice with Asthma

ABSTRACT Background Asthma is the most common chronic pulmonary disease in children. MicroRNAs (miRNAs) play a regulatory role in the occurrence and development of asthma. We aimed to explore the differential expression of miRNAs in the peripheral blood of children with asthma and identify a miRNA that can alleviate asthma inflammation. Methods We used high-throughput sequencing to analyze differences in peripheral blood miRNA between children with acute asthma and healthy children, followed by target gene prediction and functional enrichment analysis. We inhibited miR-142-3p’s expression in asthmatic mice to observe asthma symptoms. Inflammatory changes in lung tissue were assessed using hematoxylin and eosin staining and ELISA. Subsequently, the target gene of miR-142-3p was identified through a dual-luciferase reporter assay, and PTEN and AKT expression levels in mice lung tissue were determined using qPCR and western blot. Results Fifty one differentially expressed miRNAs were identified. Inhibition of miR-142-3p expression in asthmatic mice reversed the downregulation of PTEN and activation of AKT in lung tissue, while also significantly alleviating symptoms and pulmonary inflammation in the asthmatic mice. Conclusion miRNAs were differentially expressed in the peripheral blood of children with asthma. miR-142-3p regulates airway inflammation via the PTEN/AKT pathway.

Age-dependent mathematical models of ligaments and tendons

Understanding the internal structure and the underlying physical mechanisms governing the mechanical properties of ligaments and tendons, particularly the elastic modulus, across different stages of life is critical for enhancing tissue strength during growth, maturation, and aging. This knowledge is essential not only for preventing tissue failure in older adults but also for advancing the development of biomaterials that can substitute or augment ligament and tendon function across all age groups. Despite the significance of this area, a comprehensive, mechanistic understanding of the relationship between structural changes and mechanical properties over time remains largely unexplored. To date, there is a lack of detailed studies that elucidate the physical mechanisms involved in these age-related changes. The absence of such mechanistic insights highlights a significant gap in the literature, necessitating further investigation. Therefore, this research delves into the age-dependent structural and mechanical property changes in ligaments and tendons, emphasizing both growth and mature phases. Utilizing a comprehensive approach, we have developed new mathematical models that directly correlate the growth of collagen in fibrils with the increasing elastic modulus in the fibers of ligaments and tendons over time. By integrating experimental data from mouse tail tendons in published work and conducting simulations, we have observed that the cross-sectional area of collagen in fibrils and the elastic modulus of a collagen fiber increase rapidly during the growth phase and stabilize during the mature phase. Our proposed models effectively describe the trends in collagen growth and the elastic modulus of fibers in ligaments and tendons over different ages, exhibiting consistency with experimental data. Through detailed analysis, we elucidate the mechanistic relationship between collagen growth and the elastic modulus of fibers as they age. This comprehensive approach significantly enhances our understanding of the age-related structural and mechanical property changes in connective tissues, providing a robust framework for future investigations.

Environmental Factors, Occupational Hazards, and Seasonal Changes: Unveiling the Triggers of Atrial Fibrillation.

Atrial Fibrillation (AF) is the most common cardiac arrhythmia in the world, with a lifetime risk of 26% for men and 23% for women. Atrial fibrillation is a prevalent cardiac arrhythmia that is more common with increasing age. Globally, around 33.5 million people are estimated to have AF, which is anticipated to rise as the population ages. Although effective therapeutic methods exist, they are costly for the healthcare system. The search was conducted across multiple databases, including Medline, PubMed, and Google Scholar, as well as through manual searches of recognized publications and their bibliographies. Identifying modifiable risk factors for AF and implementing appropriate preventative measures may significantly improve public health and reduce healthcare costs. The development of AF has been reported to be associated with various causes, including electrical and structural changes in the atrial tissue. This article has reviewed how environmental factors, occupational hazards, and seasonal variability can affect AF. The incidence and prevalence of AF have been increasing, leading to a high lifetime risk for individuals. The available evidence indicates that seasonal variation, environmental factors, such as noise and air pollution, type of job, and altitude are all associated with an increased risk of developing AF. Although the exact mechanisms underlying these associations remain unclear, it is likely that a combination of factors, including changes in autonomic tone, inflammation, and oxidative stress, play a role. This review has highlighted the significance of assuming the role of environmental and occupational factors in the development of AF.

Relationship between flap microcirculation and hard tissue changes following alveolar ridge augmentation: a prospective case series.

To assess blood flow alterations after horizontal Guided Bone Regeneration (GBR) and to evaluate correlations between blood flow and hard tissue changes. Twelve mandibular surgical sites were involved in the current case series. GBR was carried out using a split-thickness flap design. Blood circulation was assessed with Laser Speckle Contrast Imaging at baseline as well as 1, 4, 6, 11, 13, 20, 27, and 34 days after the surgery, subsequently on a monthly basis until 6 months. Hard tissue alterations were measured horizontally and vertically using linear measurements. The first measurement point was 2 mm distal to the distal surface of the last tooth; additional measurement points were placed every 3 mm up to the 15th mm. Volumetric hard tissue loss and gain were also assessed. Baseline blood circulation was statistically significantly higher on the buccal side. On the first postoperative day, all regions presented a statistically significant decrease in blood flow circulation. The buccal-inner region presented significant ischemia on day 6. Mean volumetric hard tissue gain and loss were 712.62 ± 317.08 mm3 and 222.431 ± 103.19 mm3, respectively. Mean baseline alveolar ridge width was 4.82 ± 1.02 mm, 6 months ridge width averaged 7.21 ± 0.99 mm. Vertical resorption measured 1.24 ± 0.5 mm. Correlations between blood flow changes and hard tissue alterations were only found on Day 34 and Day 60. Laser Speckle Contrast Imaging is an efficient method to measure flap microcirculation. No correlation was found between flap microcirculation changes hard tissue and alterations.

Sex-Dependent Differences in the Elemental Composition of Internal Organs Determined via Total Reflection X-Ray Fluorescence and Inductively Coupled Plasma Optical Emission Spectroscopy

Background: Research on elemental changes in tissues and organs provides valuable information enabling better understanding of the physiological processes occurring in a living organism, as well as the pathogenesis and course of various diseases. They may also contribute to the development of new, more effective, and safer therapeutic strategies. So far, they have been carried out mainly on male individuals because of the easier planning and conducting of experiments as well as the lower variability of the results in comparison with studies involving females. Methods: The significance of incorporating both sexes in research concerning elemental alterations of tissues may be unveiled by data concerning the influence of sex on the physiological levels of selected elements in various rat organs. Therefore, here we determined and compared the levels of P, S, K, Ca, Fe, Cu, Zn, and Se in brains, hearts, kidneys, livers, and spleens taken from male and female rats. To measure the concentrations of the elements in digested tissue samples, ICP-OES and TXRF methods were utilized. Results: Significant differences between male and female rats were found for all the organs examined, and the concentrations of most of the tested elements were higher in males than females. The exception was Fe, the level of which in the kidneys and liver was higher in female rats. Sex influenced the elemental composition of spleen the most. For the brain, heart, kidneys, and liver, differences were sparse and were found mainly for the heavier elements.

A multi-omics approach identifies the key role of disorders of sphingolipid metabolism in Ang II-induced hypertensive cardiomyopathy myocardial remodeling

Hypertension-induced myocardial remodelling encompasses both structural and functional changes in cardiac muscle tissue, such as myocardial hypertrophy, fibrosis, and inflammation. These alterations not only impair the systolic and diastolic functions of the heart but also elevate the risk of cardiovascular events and heart failure. One of the primary contributors to hypertensive cardiomyopathy (HTN-CM) is the over-activation of the renin-angiotensin-aldosterone system (RAAS), which subsequently induces myocardial remodeling. Although conventional therapeutic strategies aim to suppress RAAS and slow the progression of heart failure, the primary challenge in treating HTN-CM remains the lack of sensitive and specific biomarkers for early detection of myocardial remodelling. Combined multi-omics analyses, complemented by experimental validation, offer a systematic understanding of the landscape of gene/protein/metabolite expression in HTN-CM, revealing the underlying mechanisms of angiotensin II (Ang II)-induced myocardial remodeling in HTN-CM. Transcriptomic analysis revealed that differentially expressed genes (DEGs) are implicated in sphingolipid metabolic processes and are associated with collagen synthesis and inflammatory responses, collectively contributing to myocardial remodeling in HTN-CM. Proteomic analysis demonstrated that differentially expressed proteins (DEPs) are also involved in inflammatory and fibrotic processes, with associations to sphingolipid signaling pathways, particularly manifested through elevated expression of IL6, COL4A1, FGG, FGB, CREBBP and SPHK2 proteins. Metabolomic profiling further elucidated the increased expression of bioactive sphingolipid metabolites S1P and Sa1P in the myocardium of HTN-CM. Integrative multi-omics analysis revealed that HTN-CM is primarily influenced by the sphingolipid signaling pathway, with additional associations to the HIF-1α and FoxO signaling pathways. Correlation analysis has highlighted strong associations between sphingolipids and genes/proteins related to fibrosis and inflammation, as well as their connection to the HIF-1α and FoxO signalling pathways. Furthermore, certain key indicators were validated through ELISA and Western blot analyses in both plasma and myocardial tissue. In conclusion, the findings of this study suggest that excessive Ang II may induce abnormalities in sphingolipid metabolism, resulting in increased levels of S1P in both circulating and myocardial tissues. This elevation in S1P is implicated in myocardial inflammatory and fibrotic alterations, highlighting its pivotal role in myocardial remodeling. The specific mechanism underlying the sphingolipid signaling pathway in myocardial remodeling may involve downstream biological processes, including oxidative stress and excessive mitochondrial autophagy, mediated by HIF-1α and FoxO.

Assessment of the physiological effects and safety of transpulmonary chemoembolization with doxorubicin on pulmonary tissue using a human-isolated lung perfusion model

BackgroundWhole lung transpulmonary chemoembolization using a combination of doxorubicin (DXO) and degradable starch microspheres (DSM-TPCE) might be a promising treatment option in soft tissue sarcoma. To pave the way for clinical studies, this study aimed to evaluate the short-term effects of DSM-TPCE with DXO using an ex vivo isolated lung perfusion (ILP) model.MethodsNine lung specimens retrieved from patients undergoing lobectomy underwent ex vivo ILP. In groups of three, lung specimens were either treated with sole DXO, sole DSM, or combined substances (DSM + DXO). During ex vivo ILP, histological samples were obtained from each lung every 15 min. Quantitative DXO analysis and histopathological grading of possible tissue damage using a five-point Likert scale was performed. Two-way repeated measures ANOVA tested for differences between treatment groups and changes over time.ResultsWe created a preclinical ex vivo ILP model to simulate the effects of DSM-TPCE. In histopathological analysis, only two specimens, treated with only DXO, showed an increase in parenchymal damage over time. No significant effect of time (3.3%, p = 0.305) or group (23.3; p = 0.331) was identified. Within the lung tissue, the DXO concentration ranged from 205 to 1,244 ng/g. No significant effects could be detected regarding different treatment groups (4.9% of total variation, p = 0.103).ConclusionIn an ex vivo ILP model using human lung lobes, the physiological effects of DSM-TPCE with DXO could be tested. Neither increased DXO concentrations in lung tissue nor histopathological changes indicating early lung toxicity were observed.Relevance statementAn ex vivo ILP model using human lung specimens did not show any signs of early lung toxicity after transpulmonary chemoembolization with DXO. These results support further evaluation of DSM-TPCE in phase I/II trials.Key PointsTranspulmonary chemoembolization can be investigated in an ex vivo ILP model.DSM did not increase DXO in normal lung tissue.DSM did not increase parenchymal toxicity compared to the control groups.Graphical

ULK1 methylation promotes TGF-β1-induced endometrial fibrosis via the FOXP1/DNMT1 axis.

Intrauterine adhesion (IUA) is the second most common cause of secondary infertility in women and can also lead to menstrual abnormalities and multiple adverse pregnancy outcomes. Therefore, elucidating the mechanism of its development is crucial for the prevention and treatment of IUA. This study will investigate the function and mechanism of forkhead box P1 (FOXP1)/DNA methyltransferase 1 (DNMT1)/unc-51-like autophagy activating kinase 1 (ULK1) in IUA. Expression levels of key genes were detected using western blot and quantitative - real time reverse transcription polymerase chain reaction. Cell proliferation was detected by CCK-8 and EdU staining. Transcriptional regulation relationships were detected by dual luciferase reporter gene and chromatin immunoprecipitation (ChIP) assay. Methylation station of ULK1 was detected by methylmion specific PCR (MSP). Fibrosis and pathological changes in the uterine cavity tissues were detected by Masson and hematoxylin and eosin staining. It was observed that the expression of FOXP1 and DNMT1 increased in transforming growth factor (TGF)-β1-induced cells, while ULK1 expression decreased. Downregulation of FOXP1 could inhibit human endometrial stromal cells proliferation and autophagy, as well as decrease the expression of fibrogenic factors (collagen type I alpha 1 chain [COL1A1], fibronectin [FN], and alpha-smooth muscle actin [α-SMA]). The results of MSP and ChIP experiments showed that DNMT1 promotes methylation of the ULK1 promoter region and inhibits its transcription. In an animal model, knockdown of FOXP1 alleviated pathological fibrosis and uterine adhesions. Knockdown of FOXP1 can inhibit endometrial fibrosis in IUA rats; FOXP1 could be a potential target for the treatment of IUA.

Evaluating massage therapy for radiation-induced fibrosis in rats: preliminary findings and palpation results

ABSTRACT Radiation-induced fibrosis (RIF) is a common side effect of cancer treatment, but can manifest into a devastating syndrome for which there is no preventive measure or cure. In rats who perform a repetitive work task, who left untreated develop signs and symptoms that resemble repetitive motion disorders in humans, we have shown that manual therapy prevents the development of fibrosis and other key biomarkers. The fibrosis of RIF and repetitive motion disorders has similar biomarkers. In rats, we sought to determine if manual therapy would alter key biomarkers of post-irradiation fibrosis following X-ray irradiation given to the rat forelimb. One limb of rats was given a damaging dose of X-ray irradiation. Some limbs were massaged using a protocol previously described and characterized. Serum inflammatory markers, histological assays of tissue fibrosis and nerve pathology, and electrophysiology for neuropathic discharge were assayed after 8 weeks. We also tested if an experienced therapist could identify the irradiated limb using blinded palpation at the 8 week end-point. While preliminary assays showed robust changes compared to control limbs, the other assays did not show similar pathology. Our therapist could detect each irradiated limb. Serum inflammatory markers were reduced by massage to the irradiated limb. We conclude that blinded palpation is sensitive to detect subtle changes in tissue following irradiation. In contrast to the preliminary studies, the dose of irradiation used was insufficient to induce long-lasting deep fibrosis or nerve degeneration. We suspect that a difference in housing, and thus physical activity, was the plausible reason for this difference.

Probiotics Combined with Metformin Improves Sperm Parameters in Obese Male Mice through Modulation of Intestinal Microbiota Equilibrium.

The decline in sperm parameters among obese males has attracted significant scholarly interest. The intestinal microbiota plays a crucial role in obesity, and investigating the intestinal-reproductive axis may offer a novel molecular approach to addressing the decline in male sperm parameters caused by obesity. To clarify whether probiotics, either alone or in conjunction with metformin, can enhance sperm parameters in obese male mice and assess the underlying mechanisms involved.6-week-old male mice were constructed as obese models. Probiotics and metformin were used as intervention conditions. Changes in inflammatory factors and ROS content were detected by ELISA, morphological changes in testicular and colon tissues were observed by H&E staining, changes in intestinal microbiota abundance were detected by 16SrRNA gene sequencing, and changes in metabolites such as blood glucose, blood lipids, and lipopolysaccharide were detected by biochemical testing to investigate the mechanism of probiotics, metformin, and their combination to ameliorate reproductive impairment in obese male mice. Our results revealed that high-fat diet would result in reduced testicular spermatogenic tubule hierarchy, decreased spermatogenic cell counts, decreased sperm concentration and motility, and altered abundance of intestinal microbiota, whereas the combination of probiotics and metformin could restore high-fat-mediated pathophysiological alterations thereby ameliorating spermatogenic disorders in mice.The combination of probiotics and metformin can attenuate inflammation and oxidative stress, while enhancing androgen production to improve testicular spermatogenic function by re-construction intestinal microbiota equilibrium in HFD mice.

Histological examination of rabbit tissues and internal organs during experimental infection with Trichinella spiralis larvae

The purpose of the research is to conduct a histological examination of the tissues and organs of rabbits experimentally infected with Trichinella spiralis larvae.Materials and methods. Necropsy was performed and organ and tissue samples were taken for histological studies 45 days after the experimental infection of White Giant rabbits with T. spiralis. The samples were fixed in 10% buffered formalin. Histological preparations: paraffin sections 4 μm thick, stained with hematoxylin and eosin.Results and discussion. A complete histological examination of the dermis, muscles and internal organs in experimental trichinellosis was conducted. The effect of T. spiralis larvae on the body of rabbits and the pathological changes in organs and tissues were determined. Pathological changes of an inflammatory nature were established in the heart muscle, kidneys, lungs, small intestine, spleen and muscle tissue and the muscle layer of dermis with the presence of accumulation of lymphocytes and eosinophils. Colored illustrations of the obtained sections with a detailed description are provided.

Three-dimensional quantification of soft tissue changes and its relationship to skeletal changes after Le Fort III, monobloc, and facial bipartition in syndromic craniosynostosis

To determine the effect of midface surgery on soft tissue changes and their relationship to hard tissue changes in patients with syndromic craniosynostosis. A retrospective analysis of patients who had undergone Le Fort III (LFIII), monobloc (MB), or facial bipartition (FB) was conducted. A 3D soft tissue mesh was generated from the preoperative scan and registered to the postoperative scan, after which the advancement was visualised. A total of 68 patients were included: 28 had undergone LFIII, 27 MB, and 13 FB. The included diagnoses were Apert (n = 23), Crouzon (n = 34), and craniofrontonasal syndrome (n = 11). After LFIII, most soft tissue advancement was seen around subnasale and pronasale (mean 15.1 ± 5.9 mm and 14.7 ± 5.7 mm, at age 7–12 years). After MB, a greater hard tissue than soft tissue advancement was seen for most landmarks, showing a high positive correlation. In patients undergoing FB without distraction (n = 10), mean preoperative inter-canthal distance was 48.9 mm, this reduced by 6.9 mm postoperatively. This study provides a comprehensive overview of the outcomes after midface surgery using 3D quantification for a better understanding of the soft tissue changes and their relationship to hard tissue changes.

Ameliorative effects of Turbinaria ornata extract on hepatocellular carcinoma induced by diethylnitrosamine in-vivo.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths and the fifth most common cancer worldwide. Brown algae appeared to be a rich source of efficient and safe agents against many life-threatening diseases like cancer. Thus, the scope of this study was to investigate the therapeutic effects of Turbinaria ornata against experimentally induced HCC in a rat model. Accordingly, forty male albino rats were divided into four groups. HCC was induced by intraperitoneal injection with diethylnitrosamine (DENA) followed by carbon tetrachloride (CCL4). After four weeks of DENA + CCL4 injection and two weeks of treatment with Turbinaria ornata, rats were sacrificed to collect hepatic tissue and blood samples for histopathological observations and various biochemical markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha-fetoprotein (AFP), urea, creatinine, albumin (ALB), and alkaline phosphatase (ALP). Rats that were injected for four weeks with DENA + CCL4 showed a significant increase in AFP levels, transforming growth factor-beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), as well as a high percentage of malignant changes in hepatic tissues. The extension of malignant changes in the rat liver tissues was markedly reduced using Turbinaria ornata, as the treatment displayed liver patterns similar to that of the normal control rats. Furthermore, rats with HCC fed with Turbinaria ornata extract for two weeks showed decreasing levels of TGF-β and TNF-α. These findings demonstrate that Turbinaria ornata supplement can prevent HCC development in hepatic rats; however, the exact mechanism requires further investigation.

LncRNA MALAT1 to Enhance Pyroptosis in Viral Myocarditis Through UPF1-Mediated SIRT6 mRNA Decay and Wnt-β-Catenin Signal Pathway.

Viral myocarditis (VMC) is an inflammatory disease of the myocardium caused by cardioviral infection, especially coxsackievirus B3 (CVB3), and is a major contributor to acute heart failure and sudden cardiac death in children and adolescents. LncRNA MALAT1 knockdown reportedly inhibits the differentiation of Th17 cells to attenuate CVB3-induced VMC in mice. Moreover, long non-coding RNAs (lncRNAs) interact with RNA-binding proteins (RBPs) to regulate UPF1-mediated mRNA decay. However, it remains unclear whether MALAT1 can bind to UPF1 to mediate the mRNA decay of its target genes in VMC. Herein, we aimed to explore the effect of lncRNA MALAT1 on UPF1-mediated SIRT6 mRNA decay in VMC using in vivo and in vitro experiments. CVB3-infected BABL/C mice were used as VMC models, and MALAT1 interfering adenovirus was injected to achieve MALAT1 knockdown. The heart function of the VMC mice was assessed using echocardiography. Pathological changes in myocardial tissues were assessed after hematoxylin-eosin staining. Myocardial injury and inflammation were evaluated by measuring creatine kinase isoenzyme B, cardiac troponin T, interleukin (IL)-1β, and IL-18. TUNEL staining was performed to assess apoptosis in myocardial tissues. In vitro experiments were performed using H9c2 cells after transfection and CVB3 infection. The lactic dehydrogenase release, caspase-1 activity, and IL-1β and IL-18 levels in the cellular supernatant were detected. Western blotting was performed to determine the expression of pyroptosis-related proteins (GSDMD-N, NLRP3, ASC, and Cleaved-Caspase-1) and Wnt/β-catenin signal pathway-related proteins (Wnt1, β-catenin, and p-GSK-3β). RNA immunoprecipitation and RNA stability assays assessed the relationship between MALAT1, UPF1, and SIRT6. CVB3-infected mice and H9c2 cells exhibited elevated MALAT1 and reduced SIRT6 expression. MALAT1 knockdown or SIRT6 overexpression suppressed inflammation and pyroptosis and inhibited the activation of the Wnt/β-catenin signal pathway in myocardial tissues and cells. MALAT1 enhanced the enrichment of SIRT6 mRNA by UPF1 and disturbed the stability of SIRT6 mRNA to promote the development of VMC. MALAT1 can bind UPF1 to mediate SIRT6 mRNA decay and activate the Wnt/β-catenin signal pathway in VMC.

Patterns of Gene Expression Profiles Associated with Colorectal Cancer in Colorectal Mucosa by Using Machine Learning Methods.

Colorectal cancer (CRC) has a very high incidence and lethality rate and is one of the most dangerous cancer types. Timely diagnosis can effectively reduce the incidence of colorectal cancer. Changes in para-cancerous tissues may serve as an early signal for tumorigenesis. Comparison of the differences in gene expression between para-cancerous and normal mucosa can help in the diagnosis of CRC and understanding the mechanisms of development. This study aimed to identify specific genes at the level of gene expression, which are expressed in normal mucosa and may be predictive of CRC risk. A machine learning approach was used to analyze transcriptomic data in 459 samples of normal colonic mucosal tissue from 322 CRC cases and 137 non-CRC, in which each sample contained 28,706 gene expression levels. The genes were ranked using four ranking methods based on importance estimation (LASSO, LightGBM, MCFS, and mRMR) and four classification algorithms (decision tree [DT], K-nearest neighbor [KNN], random forest [RF], and support vector machine [SVM]) were combined with incremental feature selection [IFS] methods to construct a prediction model with excellent performance. The top-ranked genes, namely, HOXD12, CDH1, and S100A12, were associated with tumorigenesis based on previous studies. This study summarized four sets of quantitative classification rules based on the DT algorithm, providing clues for understanding the microenvironmental changes caused by CRC. According to the rules, the effect of CRC on normal mucosa can be determined.

Moxibustion inhibits the macrophage M1 polarization toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B signaling pathway by regulating T-cell immunoglobulin and mucin-containing protein-3 in rheumatoid arthritis.

To explore whether moxibustion exerts therapeutic effects on rheumatoid arthritis (RA) by regulating the expression of T-cell immunoglobulin and mucin-containing protein-3 (TIM-3) and subsequently modulating the macrophage M1 polarization toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) signaling pathway. We utilized moxibustion treatment in RA rat models using the Zusanli (ST36) and Shenshu (BL23) acupoints. Hematoxylin and eosin (HE) staining was used to observe the pathological changes of the synovial tissue under a section light microscope, and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease. Enzyme-linked immunosorbent assay (ELISA) was applied to verify the efficacy of moxibustion in reducing inflammation. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of the TIM-3/TLR4-MyD88-NF-κB signaling pathway-related molecules, and Western blot was used to detect the contents of synovial NF-κB. We established the Freund's complete adjuvant (FCA)-induced RA model in rats. The expression level of M1 polarization signaling pathway TLR4-MyD88-NF-κB and the inflammatory factors interleukin-12(IL-12), tumor necrosis factor alpha (TNF-α), and tumor necrosis factor beta (TNF-β) were significantly increased in the RA model. After moxibustion treatment, the expression level of TLR4-MyD88-NF-κB was significantly decreased, and the inflammatory factors IL-12, TNF-α, and TNF-β were decreased, but the expression level was significantly increased in the RA model. When TIM-3 expression was inhibited, the expression level of TLR4-MyD88-NF-κB, and the inflammatory factors IL-12, TNF-α, and TNF-β were not suppressed, even after moxibustion treatment. Moxibustion regulates the key target TIM-3 by acting on the Zusanli (ST36) and Shenshu (BL23) points, thereby inhibiting the M1 polarization of macrophages; that is, it inhibits the TLR4-MyD88-NF-κB signaling pathway, and finally achieves alleviation of pathological changes and anti-inflammatory effects.

Alterations in the nutrient composition, muscle quality, and proteomics of two Sepiidae species (Sepiella maindroni and Sepia esculenta) during storage

The present study compared muscle protein characteristics between Sepiella maindroni (S. maindroni) and Sepia esculenta (S. esculenta). We analyzed the nutrient composition, myofibrillar protein properties, and proteomic changes in muscle tissue under freezing conditions. Amino acid analysis revealed 17 hydrolyzed amino acids in both species’ muscle tissues, with tryptophan identified as the first limiting amino acid. Essential amino acids (EAAs) constituted more than 31% of total amino acids (TAAs), aligning closely with the FAO/WHO recommended ideal protein pattern. The Essential Amino Acid Index (EAAI) for S. maindroni was high at 82.99. Twenty fatty acids were identified in both species, with total contents of C20:5n-3 (EPA) and C22:6n-3 (DHA) exceeding 40%. S. maindroni had significantly more such fatty acids than S. esculenta. During the freezing process, the total sulfhydryl content and Ca2+-ATPase activity of both species showed a decreasing trend, while carbonyl content exhibited an overall increase. After 60 days of freezing, the total sulfhydryl content and Ca2+-ATPase activity in the muscles of both species decreased to minimum levels. Compared to fresh samples, both species’ muscle tissues exhibited varying degrees of deterioration in microscopic structure after 60 days of freezing. A total of 350 differentially expressed proteins (DEPs) comprising 208 upregulated and 142 downregulated proteins were identified in S. maindroni and S. esculenta. After 60 days of freezing, 322 DEPs, including 181 upregulated and 141 downregulated proteins, were detected in both species. COG functional classification indicated that low-temperature storage affected DEPs in the muscle tissue, influencing the flavor, texture, and protein functionality of the species.

Schisandrin B Inhibits LPS-Induced Endometritis Through Attenuating Ferroptosis via AMPK/PGC1α/Nrf2 Signalling Pathway.

Endometritis is one of the common reproductive diseases in human and animal. In recent years, a number of studies have found that Schisandra B (Sch B), as a natural Chinese medicine extract, has antioxidant, anti-inflammatory and other biological activities. Based on the above, in this study, mice were used to conduct an invivo experiment to investigate the effect and mechanism of Sch B on lipopolysaccharide (LPS)-induced endometritis. Haematoxylin and eosin (H&E) staining was used to detect the pathological changes of uterine tissue and western blot was used to detect the expression levels of signalling pathways and key genes for ferroptosis. The results showed that Sch B significantly inhibited the pathological injury of uterine tissue, myeloperoxidase (MPO) activity, the activation of NF-κB pathway and the production of TNF-α and IL-1β. Furthermore, Sch B effectively inhibited ferroptosis by inhibiting malondialdehyde (MDA) and iron production and promoting the expression of ferroptosis suppressor genes GPX4 and ferritin. In conclusion, Sch B inhibited LPS-induced endometritis through alleviating inflammatory response and ferroptosis via AMPK/PGC1α/Nrf2 signalling pathway.

Effect of Curcumin-Mediated miR-449 on Diabetic Nephropathy

This study assessed the mechanism for curcumin-mediated miR-449 regulating PACS-2 in diabetic nephropathy under nursing intervention. A diabetic nephropathy model was constructed, in which rats were fasted for 12 hours before experiments and injected with Streptozotocin (STZ) at a ratio of 45–65 mg/kg (30–60 mg STZ). When the rats aged 8 weeks, they were given intraperitoneal injection of curcumin and tissue histological morphology was detected to ensure successful model construction. HE staining observed the morphological changes in renal tissue, while immunohistochemistry detected the expression of PACS-2 and PACS-2 related proteins. Nursing intervention could reduce serum creatinine, fasting blood glucose, urea nitrogen and proteinuria levels. After nursing intervention, the levels of IL-6, hs-CRP and TNF-α in patients were significantly decreased (p < 0.05), and miR-499 expression increased after nursing intervention. After curcumin treatment, the red staining of entire kidney cytoplasm in the control and experimental groups became lighter. Moreover, the expression of miR-449 in the kidney tissue was significantly increased after curcumin treatment. Since PACS-2 plays an important role in kidney injury, curcumin largely normalized kidney injury as shown by serum BUN levels after curcumin treatment in the rat model. Turmeric, a traditional Chinese medicine, has a bitter taste and warm nature. It might facilitate blood circulation and remove blood stasis, and relieving chest pain and heartache. Curcumin as the main active ingredient of turmeric, has been proven to inhibit the abnormal proliferation of diabetic nephropathy. Under the influence of effective nursing care, the patient’s physical condition was improved, which was mainly reflected in the related inflammatory indicators. Studies have shown that fibronectin, which is an important indicator for PACS-2, plays a decisive role in fibrosis. Our testing found that, curcumin significantly reduced the expression of PACS-2 during treatment. Nursing intervention can therefore effectively improve inflammatory response and renal function of diabetic nephropathy through curcumin-mediated miR-449 regulation of PACS-2.