Proliferation Of Connective Tissue Research Articles

Histological organization of the spleen of rats under conditions of acute intoxication with viper venom Vipera berus berus

The immune system plays an important role in the body's response to numerous environmental factors, including snake venom toxins. The composition of snake venom and the specifics of its effect on the human body are quite diverse. The predominance of one or another component of the toxin becomes decisive for the appearance of complications or even death. The study aims to study the peculiarities of the histological organization of the spleen of rats under conditions of acute intoxication with Vipera berus berus viper venom. Experimental studies were carried out on white, non-linear male rats. The animals were conditionally divided into a control and an experimental group of 10 individuals. Experimental rats were injected intraperitoneally with a semi-lethal dose (LD50) (1.576 mg/g-1) of Vipera berus berus venom in a physiological solution. Animals of the control group were injected intraperitoneally with only a physiological solution. Rats were removed from the experiment 24 hours after exposure to the poison and anaesthetised by cervical dislocation. Spleen samples were taken for microscopic examination. Fixation of the material and preparation of paraffin blocks were carried out according to generally accepted methods. Histological preparations of the spleen were stained with hematoxylin and eosin. Histological preparations were studied using an SEO SСAN light microscope. Acute intoxication with Vipera berus berus viper venom was associated with disorganization of the white pulp of the spleen of experimental animals, which manifested itself in the form of a loss of clarity and orderliness of the placement of its structural elements, poor visualization of the marginal zone of lymphoid nodules. An increase in the number of lymphoblasts characterized the germinal centres. Areas of spleen tissue destruction and hemorrhage were noted in the red pulp of the organ. The presence of foci of lymphocyte apoptosis, thickening of trabeculae, stasis and sludge of erythrocytes in the lumen of trabecular veins was also observed. Thus, under the influence of Vipera berus berus venom, disorganization of the white pulp is observed at the structural level of the rat spleen, and areas of organ destruction, lymphocyte apoptosis, and connective tissue proliferation are noted in the red pulp.

An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts.

Malignant fibroblasts (MFs) are widely present in various diseases and are characterized by connective tissue proliferation; these cells act as a physical barrier that severely limits drug delivery and affects disease outcomes. Based on this, we constructed the smart, integrated, theranostic, targeted lipid nanoprobe HMME-RG3@PFH to overcome the bottleneck in the early diagnosis and treatment of MF-related diseases. The protein glucose transporter protein 1 (GLUT-1) is overexpressed on MFs, and its ideal substrate, ginsenoside RG3 (RG3), significantly enhances the targeted uptake of HMME-RG3@PFH by MFs in a hypoxic environment and endows the nanomaterial with stealthiness to prolong its circulation. Perfluorohexane (PFH), a substance that can undergo phase change, was encapsulated in the lipid core and vaporized for ultrasound-enhanced imaging under low-intensity focused ultrasound (LIFU) irradiation. Moreover, hematoporphyrin monomethyl ether (HMME) was loaded into the lipid bilayer for photoacoustic molecular imaging and sonodynamic therapy (SDT) of MFs under the combined effects of LIFU. Additionally, HMME-RG3@PFH instantaneously burst during visualization to promote targeted drug delivery. In addition, the increased number of exposed RG3 fragments can regulate the MFs to enter a quiescent state. Overall, this nanoplatform ultimately achieves dual-modal imaging with targeted and precise drug release for visualization and synergistic amplification therapy, providing a new possibility for the early diagnosis and precise treatment of MF-related diseases.

Does Collagen Membrane Coverage Offer any Advantage for Lateral Window Sinus Augmentation? A Histologic and Histomorphometric Analysis.

We aimed to determine whether collagen membrane coverage in maxillary sinus floor elevation surgery, provides an advantage regarding bone regeneration. This randomized clinical trial included all healthy adults presented for dental implant placement in the posterior edentulous maxilla at the Maxillofacial Surgery Department of Mashhad Dental School, Mashhad, Iran from 2021-2022. Participants were candidates for sinus floor elevation surgery. Patients were randomly allocated to control (with membrane) and test (without membrane) groups. Surgery was performed through the lateral window technique and using allograft particles. According to the assigned study group; either a collagen membrane was placed over the osteotomy window or it was left uncovered. Six months after surgery when patients were recalled for implant placement, a bone specimen was obtained and sent for histologic and histomorphometric analysis. The predictor variable was the use of collagenous membrane and the outcome variables were the amount of newly formed bone, native bone, and connective tissue. A total of 30 consecutive patients, with a mean age of 46.33±7.25 years completed the study. Histomorphometric measurements, six months after augmentation revealed that the mean area of connective tissue was significantly less in the group with membrane coverage (P=0.015). The area of newly formed bone was significantly greater in sites covered with a collagen membrane compared to grafted but uncovered sites; (P <0.001). Covering the lateral osteotomy window with a bioabsorbable collagenous membrane is able to significantly enhance vital bone formation and decrease connective tissue proliferation.

RELATO DE CASO: HIPERPLASIA MAMÁRIA EM FELINO MACHO

Feline mammary fibroepithelial hyperplasia (FMFH) is a benign, non-neoplastic condition that primarily affects young female cats, usually less than two years old. It is characterized by the proliferation of mammary duct epithelium and periductal connective tissue, associated with the hormonal effects of endogenous and exogenous progestogens. Although more common in females during pregnancy, pseudopregnancy, or early estrus, it can also occur in males after prolonged treatment with progestogens. This report describes the case of an uncastrated male cat in which two small nodules were found in the abdominal region, and subsequently, five more nodules were detected in the mammary region via ultrasound. These nodules underwent fine-needle aspiration cytology, revealing well-differentiated epithelial and mesenchymal cells, suggestive of fibroadenomatous mammary hyperplasia. The animal then underwent castration and, the next day after the procedure, the nodules completely disappeared.

Revealing a cancer-associated fibroblast-based risk signature for pancreatic adenocarcinoma through single-cell and bulk RNA-seq analysis.

Proliferation of stromal connective tissue is a hallmark of pancreatic adenocarcinoma (PAAD). The engagement of activated cancer-associated fibroblasts (CAFs) contributes to the progression of PAAD through their involvement in tumor fibrogenesis. However, the prognostic significance of CAF-based risk signature in PAAD has not been explored. The single-cell RNA sequencing (scRNA-seq) data sourced from GSE155698 within the Gene Expression Omnibus (GEO) database was supplemented by bulk RNA sequencing data from The Cancer Genome Atlas (TCGA) and microarray data retrieved from the GEO database. The scRNA-seq data underwent processing via the Seurat package to identify distinct CAF clusters utilizing specific CAF markers. Differential gene expression analysis between normal and tumor samples was conducted within the TCGA-PAAD cohort. Univariate Cox regression analysis pinpointed genes associated with CAF clusters, identifying prognostic CAF-related genes. These genes were utilized in LASSO regression to craft a predictive risk signature. Subsequently, integrating clinicopathological traits and the risk signature, a nomogram model was constructed. Our scRNA-seq analysis unveiled four distinct CAF clusters in PAAD, with two linked to PAAD prognosis. Among 207 identified DEGs, 148 exhibited significant correlation with these CAF clusters, forming the basis of a seven-gene risk signature. This signature emerged as an independent predictor in multivariate analysis for PAAD and demonstrated predictive efficacy in immunotherapeutic outcomes. Additionally, a novel nomogram, integrating age and the CAF-based risk signature, exhibited robust predictability and reliability in prognosticating PAAD. Moreover, the risk signature displayed substantial correlations with stromal and immune scores, as well as specific immune cell types. The prognosis of PAAD can be accurately predicted using the CAF-based risk signature, and a thorough analysis of the PAAD CAF signature may aid in deciphering the patient's immunotherapy response and presenting fresh cancer treatment options.

Angiotensin II depends on hippo/YAP signaling to reprogram angiogenesis and promote liver fibrosis

Liver fibrosis is a chronic pathological process in which the abnormal proliferation of connective tissue is induced by various pathogenic factors. During the process of fibrosis, excessive angiogenesis is observed. Physiological angiogenesis has the potential to impede the progression of liver fibrosis through augmenting matrix metalloenzyme activity; however, pathological angiogenesis can exacerbate liver fibrosis by promoting collagen accumulation. Therefore, a key scientific research focus in the treatment of liver diseases is to search for the “on-off” mechanism that regulates angiogenesis from normal proliferation to pathological proliferation. In this study, we found that excessive angiogenesis appeared during the initial phase of hepatic fibrosis without mesenchymal characteristics. In addition, angiogenesis accompanied by significant endothelial-to-mesenchymal transition (EndMT) was observed in mice after the intraperitoneal injection of angiotensin II (Ang II). Interestingly, the changes in Yes-associated protein (YAP) activity in endothelial cells (ECs) can affect the regulation of angiogenesis by Ang II. The results of in vitro experiments revealed that the regulatory influence of Ang II on ECs was significantly attenuated upon suppression of YAP activity. Furthermore, the function of Ang II in regulating angiogenesis during fibrosis was investigated in liver-specific transgenic mice. The results revealed that Ang II gene deletion could restrain liver fibrosis and EndMT. Meanwhile, Ang II deletion downregulated the profibrotic YAP signaling pathway in ECs. The small molecule AT1R agonist olmesartan targeting Ang II-YAP signaling could also alleviate liver fibrosis. In conclusion, this study identified Ang II as a pivotal regulator of EndMT during the progression of liver fibrosis and evaluated the therapeutic effect of the Ang II-targeted drug olmesartan on liver fibrosis.

Molecular epidemiological studies of Leucocytozoon caulleryi in commercial layer flocks in Southern peninsular India reveal the presence of new subclusters.

The Leucocytozoon parasites are one of the important protozoa species affecting domestic poultry and wild birds. Though there are frequent reports about the incidence of Leucocytozoon in wild birds, the information regarding the occurrence of commercial poultry is underestimated. From October 2015 to August 2022, ailing and dead birds from 39 commercial layer flocks were submitted to the Poultry Disease Diagnosis and Surveillance Laboratory, Namakkal, with a history of brief illness, followed by mortality with oozing of blood from oro-nasal orifice. The presence of Leucocytozoon caulleryi was confirmed in all the flocks by laboratory examination and PCR. All the Leucocytozoon-positive cases were reported after heavy rainfall and the affected farms were inhabited with Culicoides flies. The infected birds were dull and depressed, exhibited labored breathing, and blood-tinted ropy mucous from the oro-nasal cavity. Necropsy examination revealed pale-anaemic comb and wattles, massive haemorrhagic clot over the surface of the kidney, peritoneum, and trachea, and scattering of greyish-white/reddish military megaloschizonts throughout the serosa of viscera and skeletal muscles. Histopathological examination revealed many spherical cysts or megaloschizonts in the intestine, pancreas, gizzard, spleen, liver, kidney, heart, and breast muscles. The cysts were deeply seated within the above organ's parenchyma or embedded in the serosa. There was extensive connective tissue proliferation with mononuclear cell infiltration around the cyst. Leucocytozoon-specific DNA was detected in all the flocks by PCR. Phylogenetic analysis of the cytochrome b gene of L. caulleryi reported from various parts of the world revealed that L. caulleryi is grouped into two major clusters (Cluster I & II). Further, Indian L. caulleryi sequences fall under sub-cluster I and II along with L. caulleryi reported from Taiwan, Egypt, China, Myanmar, Japan, South Korea, and Thailand.

Discovery of Novel Peptide Antagonists Targeting GPR55 for Liver Inflammation and Fibrosis.

Liver fibrosis is a condition characterized by aberrant proliferation of connective tissue in the liver resulting from diverse etiological factors. G protein-coupled receptor GPR55 has recently been identified as a regulator of liver diseases. Herein, we report the discovery of a cyclic peptide P1-1 that antagonizes GPR55 and suppresses collagen secretion in hepatic stellate cells. The alanine scanning and docking study was carried out to predict the binding mode and allowed for further structural optimization of peptide antagonists for GPR55. The subsequent in vivo study demonstrated that P1-1 ameliorates CCl4-induce and MCD-diet-induce acute liver inflammation and fibrosis. Further study indicates that P1-1 reduces reactive oxygen species (ROS) production, attenuates ER stress, and inhibits mitochondria-associated hepatocyte apoptosis. In this work, we provided the first successful example of antagonizing GPR55 for liver inflammation and fibrosis, which validates GPR55 as a promising target for the treatment of liver fibrosis and affords a high-potent GPR55 antagonist P1-1 as a potential therapeutic candidate.

Five-blade scratcher for treating severe rhinophyma: A retrospective study.

Rhinophyma, a late-stage subtype of rosacea, is characterized by excessive sebaceous glands and connective tissue proliferation. Patients may experience respiratory disturbances and psychological distress that significantly affect their quality of life when excessive nasal hyperplasia obstructs the external nasal valves. Surgery is the treatment of choice for rhinophyma. However, excessive bleeding, scarring, pigmentation, and high recurrence rates frequently characterize current surgical methods. To evaluate the clinical effectiveness and recurrence rates after treating severe rhinophyma with the five-blade scratcher. This study retrospectively analyzed the clinical records of 28 patients with severe rhinophyma rosacea. The Global Flushing Severity Score (GFSS), Clinician Erythema Assessment (CEA), Rhinophyma Severity Index (RHISI), Glasgow Benefit Inventory (GBI), and satisfaction scores were used to assess the recovery of patients at 6 months and 5 years, with the recurrence rate calculated at 5 years postoperatively. In addition, the levels of pro-inflammatory factors (TNF-α, IL-1β, and IL-6) in the serum of patients before and after surgery were detected by ELISA. The GFSS, CEA, and RHISI scores at 6 months and 5 years postoperatively were significantly lower than those preoperatively (P < 0.001 for both periods). Five-blade scratcher treatment greatly benefits patients as demonstrated by the GBI and patient satisfaction. A small number of patients (7/28, 25%) reported recurrence after surgical treatment for rhinophyma in our department that was not more serious than before treatment. The expression of pro-inflammatory factors (TNF-α, IL-1β, and IL-6) in the patient's serum was significantly reduced after surgery of five-blade scratcher. The five-blade scratcher treatment demonstrates notable advantages, including simplicity, safety, efficacy, and cost-effectiveness, coupled with reduced bleeding, minimized scarring, lower recurrence rates, reduced the level of pro-inflammatory factors and improved patient satisfaction. Consequently, this therapeutic modality exhibits a viable option for individuals afflicted with severe rhinophyma.

Glycyrrhizic acid ameliorates hepatic fibrosis by inhibiting oxidative stress via AKR7A2

BackgroundHepatic fibrosis is a reversible pathological phenomenon caused by the abnormal proliferation of connective tissues in the liver for self-repair after persistent liver injury. Among these tissues, the activation status of hepatic stellate cells (HSCs) is crucial. Glycyrrhizic acid (GA) agents have been proven to have excellent anti-fibrosis effects, but their targets are unclear. PurposeTo investigate the anti-hepatic fibrosis effect of GA and its target in activated HSCs. MethodsA mouse model of hepatic fibrosis was prepared with 20 % carbon tetrachloride (CCl4) and GA was administered continuously for 4 weeks. Subsequently, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅲ procollagen peptide (P III P), laminin (LN), hyaluronic acid (HA), and type Ⅳ collagen (Col Ⅳ) were measured. Liver tissues were subjected to hematoxylin and eosin (HE), Masson, and Sirius red staining and proteome sequencing analysis. Based on LX-2 cells, activity-based protein profiling (ABPP) was used to investigate the potential targets of GA, which was further validated by the cellular thermal shift assay (CETSA), immunofluorescence co-localization, molecular docking, small interfering RNA (siRNA) and western blot (WB) assays. ResultsIn vivo, GA significantly reduced serum ALT, AST, HA, P III P, Col IV, and LN levels. HE, Masson, and Sirius red staining showed that GA significantly ameliorated hepatic inflammatory response and collagen deposition in CCl4-treated mice. Proteome sequencing results showed that GA mainly regulated glutathione S-transferase family members involved in glutathione metabolism. In vitro, GA significantly inhibited LX-2 cell proliferation and reduced reactive oxygen species accumulation. ABPP suggested that aldo-keto reductase family 7 member A2 (AKR7A2) was the major binding protein of GA in LX-2 cells. CETSA, fluorescence co-localization, molecular docking, and surface plasmon resonance further validated GA binding to AKR7A2. The WB results showed that GA up-regulated AKR7A2 expression both in vitro and in vivo and was corroborated by siRNA experiments. ConclusionGA targeted AKR7A2 in LX-2 cells to defend against sustained oxidative stress injury, thereby inhibiting the proliferation of activated HSCs and reversing hepatic fibrosis.

Atherogenic Effect of Homocysteine, a Biomarker of Inflammation and Its Treatment.

Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Ischemic stroke and heart disease, coronary heart disease, and cardiovascular disease are events resulting from long-lasting and silent atherosclerosis. This paper deals with the synthesis of homocysteine (Hcy), causes of HHcy, mechanism of HHcy-induced atherosclerosis, and treatment of HHcy. Synthesis and metabolism of Hcy involves demethylation, transmethylation, and transsulfuration, and these processes require vitamin B 6 and vitamin B 12 folic acid (vitamin B 9 ). Causes of HHcy include deficiency of vitamins B 6 , B 9 , and B 12 , genetic defects, use of smokeless tobacco, cigarette smoking, alcohol consumption, diabetes, rheumatoid arthritis, low thyroid hormone, consumption of caffeine, folic acid antagonist, cholesterol-lowering drugs (niacin), folic acid antagonist (phenytoin), prolonged use of proton pump inhibitors, metformin, and hypertension. HHcy-induced atherosclerosis may be mediated through oxidative stress, decreased availability of nitric oxide (NO), increased expression of monocyte chemoattractant protein-1, smooth muscle cell proliferation, increased thrombogenicity, and induction of arterial connective tissue. HHcy increases the generation of atherogenic biomolecules such as nuclear factor-kappa B, proinflammatory cytokines (IL-1β, IL-6, and IL-8), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selection), growth factors (IGF-1 and TGF-β), and monocyte colony-stimulating factor which lead to the development of atherosclerosis. NO which is protective against the development of atherosclerosis is reduced by HHcy. Therapy with folic acid, vitamin B 6 , and vitamin B 12 lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B 6 , vitamin B 12 , omega-3 fatty acid, and green coffee extract reduce Hcy. Abstaining from drinking coffee and alcohol, and smoking also reduces blood levels of Hcy. In conclusion, HHcy induces atherosclerosis by generating atherogenic biomolecules, and treatment of atherosclerosis-induced diseases may be by reducing the levels of Hcy.

Physiological and biochemical studies of young sterlet sturgeon (Acipenser ruthenus L.) in the lower reaches of the Volga river

In conditions of a decrease in the number of rolled sturgeon larvae in the lower reaches of the Volga River, an urgent issue is the study of the physiological and biochemical parameters of the fish organism. The purpose of this work is to conduct physiological and biochemical studies of juvenile sterlet (Acipenser ruthenus L, 1758). The study of fish was carried out using the methods of classical histology and biochemistry. The degree of damage to the gills and liver was assessed on a scale from 1 to 5 points. The content of total lipids and water-soluble protein in the muscle tissue of sterlet fingerlings was studied as biochemical parameters. The morphological picture of the gills of 80% of the fish corresponded to a weakly pronounced character of changes (2 points), while in others it was characterized by the presence of a borderline state between weakly pronounced changes and moderate injuries (2–3 points). Six types of disorders were found in the gills: hyperplasia of the respiratory epithelium of lamellae, dilation of the blood vessel of the filament, goblet-shaped swellings of the apical part of the filament, invasions, expansion of the apical part of the lamellae, proliferation of connective tissue of lamellae. In the liver of 80% of fish, a borderline state was recorded between mild changes and moderate damage (2–3 points), in 13.3% of individuals the liver had mild damage (2 points), in 6.7% there were medium damage (3 points). Four types of disorders were found in the liver of juvenile sterlet: fullness of the liver capillaries, pronounced venous fullness, cavities, capillary dilation. In the muscle tissue of fingerlings, the concentrations of total lipids were in the range of 1.39–5.28%, and water-soluble protein — 45.59–57.97 mg/g. The study of the physiological and biochemical parameters of juvenile sturgeon in the lower reaches of the Volga River is very important for the biology of the species and monitoring the natural reproduction of these valuable fish species.

Biological Response of the Peri-Implant Mucosa to Different Definitive Implant Rehabilitation Materials.

Sealing the peri-implant tissue is a determining factor for long-term implant survival. In the transmucosal region, the cervical fraction of the prosthetic crown is in contact with these tissues, so mucointegration will also be influenced by the biomaterial used for the prosthetic restoration. This study aims to compare the tissue response generated by definitive restorative materials and polymeric materials from a histological point of view. This study performed an observational prospective cohort study in which biopsies of the peri-implant mucosa were taken after placement of implant-supported prosthetic restorations made of different materials (zirconium oxide, lithium disilicate, and PMMA). A statistically significant difference was observed in the increase in the thickness of the non-keratinized epithelium when comparing the definitive materials (zirconium oxide/lithium disilicate) vs. the provisional material (PMMA) and in the number of collagen fibers when comparing zirconium oxide and lithium disilicate. This study found that zirconia is the material that presents the most adequate biological response of peri-implant tissues. It shows a lower intensity of inflammatory cellular content, a total normality in the number of collagen fibers (the arrangement of the fibers is normal in 90% of the cases), and vascular proliferation of connective tissue in 83% of the cases. These parameters make it a material with a predictable response. Similarly, only the following slight statistically significant differences between the definitive and provisional materials are observed, indicating that the biological response generated by the provisional material (PMMA) is not very different from that obtained with the placement of the definitive restoration.

Acute Toxicity and Hepatoprotective Influence of Hypericum perforatum Against Thioactamid-Induced Liver Fibrosis in Rats

Background: Hypericum perforatum (MEHP) is a broadly used therapeutic plant exhibiting numerous bioactivities. The present study evaluates acute toxicity and hepatoprotective effects of MEHP against thioacetamide (TAA)-induced liver injury in rats. Methods: The toxicity trial included a single oral administration of 2000 and 5000 mg/kg to rats. In the hepatoprotective experiment, 30 adult rats were arbitrarily clustered into 5 groups: Normal (A) and TAA control rats (B) treated with daily distilled water; reference rats received 3 oral doses/week of 50 mg/kg silymarin; D and E, rats received daily doses of 250 and 500 mg/kg MEHP, respectively. In addition, group B-E received 3 injections of 200 mg/kg TAA in a week for 60 days. Results: The results have shown a lack of any toxic signs in rats following oral administration of up to 5000 mg/kg. The hepatoprotective evaluations revealed a noticeably lower hepatic injury in MEHP-treated rats shown by reduced liver index and hepatocyte proliferation. Histopathological evaluation (H&amp;E and Masson trichrome stains) showed a significant inhibitory potential of MEHP on the incidence rate of hepatic lesions represented by decreased liver necrosis and lower fibrous connective tissue proliferation initiated by TAA in rats. MEHP treatment meaningfully decreased proliferating cell nuclear antigen and α-SMA (myofibroblasts) in liver parenchymal tissues as well as improved redox (up-regulated SOD, CAT, GPx, and down-regulated MDA) and inflammatory state (decreased serum TNF-α and IL-6 cytokines) compared to fibrosis control rats. In addition, MEHP treatment caused significant restoration of serum liver biomarkers (enzymes and proteins) against TAA-induced hepatotoxicity. Conclusion: The present hepatoprotectives of MEHP could be attributed to its chemical contents (hypericin, hyperforin, quercitrin, and p-coumaric acid) that may validate it as a therapeutic additive for liver fibrosis after some pharmacological evaluations.

An insight into the epidemiology of foodborne zoonotic fascioliasis in small ruminants in northwestern region of Bangladesh.

Fascioliasis is one of the most common foodborne zoonotic infection of ruminants in Bangladesh. To estimate the prevalence and associated risk factors of fascioliasis and extent of liver damage, 825 livers of sheep and goats were randomly inspected during onsite slaughterhouse visiting in Naogaon, Natore, Rajshahi and Joypurhat districts. The overall prevalence of fascioliasis was 25.09% and significantly (P = 0.008) higher in goats (26.11%) than sheep (24.00%). During gross inspection, Fasciola infected livers were increased in size, fibrosed, fatty, multiple white or reddish necrotic foci on the parietal surface, hard to cut, calcified, and numerous mature and immature flukes were also observed. In histoarchitecture, inflammatory cell infiltration in the hepatic parenchyma and periportal area, fibrous connective tissue proliferation around necrotic area, hyperplastic bile duct, congestion, and primary biliary cirrhosis were seen in acute and chronic fascioliasis. Epidemiological investigations revealed that fascioliasis was higher in goats than sheep. Age, sex, BCS and season were found to have statistically significant associations with fascioliasis in goats. In case of sheep, age (OR = 5.8671; 95% CI: 2.9482-11.6757, P < 0.0001), sex (OR = 3.7317; 95% CI: 1.9052-7.3094, p < 0.0001), BCS (OR = 6.0346; 95% CI: 1.7986-20.2472, p < .0001), and season (OR = 8.2308; 95% CI: 3.9922-16.9693, p = < .0001) were also found to have statistically significant associations with fascioliasis. Results of the study can help for molecular epidemiology of fascioliasis in small ruminants to plan fluke control programs for safe food production.

The effect of neuromuscular electrical stimulation on the human skeletal muscle transcriptome.

The influence on acute skeletal muscle transcriptomics of neuromuscular electrical stimulation (NMES), as compared to established exercises, is poorly understood. We aimed to investigate the effects on global mRNA-expression in the quadriceps muscle early after a single NMES-session, compared to the effects of voluntary knee extension exercise (EX), and to explore the discomfort level. Global vastus lateralis muscle gene expression was assessed (RNA-sequencing) in 30 healthy participants, before and 3 h after a 30-min session of NMES and/or EX. The NMES-treatment was applied using textile electrodes integrated in pants and set to 20% of each participant's pre-tested MVC mean (±SD) 200 (±80) Nm. Discomfort was assessed using Visual Analogue Scale (VAS, 0-10). The EX-protocol was performed at 80% of 1-repetition-maximum. NMES at 20% of MVC resulted in VAS below 4 and induced 4448 differentially expressed genes (DEGs) with 80%-overlap of the 2571 DEGs of EX. Genes well-known to be up-regulated following exercise, for example, PPARGC1A, ABRA, VEGFA, and GDNF, were also up-regulated by NMES. Gene set enrichment analysis demonstrated many common pathways after EX and NMES. Also, some pathways were exclusive to either EX, for example, muscle tissue proliferation, or to NMES, for example, neurite outgrowth and connective tissue proliferation. A 30-min NMES-session at 20% of MVC with NMES-pants, which can be applied with an acceptable level of discomfort, induces over 4000 DEGs, of which 80%-overlap with DEGs of EX. NMES can induce exercise-like molecular effects, that potentially can lead to health and performance benefits in individuals who are unable to perform resistance exercise.

Phillygenin Inhibits TGF-β1-induced Hepatic Stellate Cell Activation and Inflammation: Regulation of the Bax/Bcl-2 and Wnt/β-catenin Pathways.

Hepatic fibrosis (HF), a precursor to cirrhosis and hepatocellular carcinoma, is caused by abnormal proliferation of connective tissue and excessive accumulation of extracellular matrix in the liver. Notably, activation of hepatic stellate cells (HSCs) is a key link in the development of HF. Phillygenin (PHI, C21H24O6) is a lignan component extracted from the traditional Chinese medicine Forsythiae Fructus, which has various pharmacological activities such as anti-inflammatory, antioxidant and anti-tumour effects. However, whether PHI can directly inhibit HSC activation and ameliorate the mechanism of action of HF has not been fully elucidated. Therefore, the aim of the present study was to investigate the in vitro anti-HF effects of PHI and the underlying molecular mechanisms. Transforming growth factor-β1 (TGF-β1)-activated mouse HSCs (mHSCs) and human HSCs (LX-2 cells) were used as an in vitro model of HF and treated with different concentrations of PHI for 24h. Subsequently, cell morphological changes were observed under the microscope, cell viability was analyzed by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and the mechanism of anti-fibrotic effect of PHI was explored by immunofluorescence, ELISA, RT-qPCR and western blot. The results showed that PHI suppressed the proliferation of TGF-β1-activated mHSCs and LX-2 cells, arrested the cell cycle at the G0/G1 phase, decreased the levels of α-SMA, Collagen I, TIMP1 and MMP2 genes and proteins, and promoted apoptosis in activated mHSCs and LX-2 cells. Besides, PHI reduced the expression of inflammatory factors in activated mHSCs and LX-2 cells, suggesting a potential anti-inflammatory effect. Mechanically, PHI inhibited TGF-β1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/β-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF.

Histological Assessment of the Effect Laser Irradiation on Full-Thickness Skin Wound Healing in Rabbits Models

Since there is currently no ideal treatment, wound healing impairment is a significant clinical challenge that is the subject of ongoing research into effective wound healing strategies. As a result, it has been demonstrated that low level laser therapy (LLLT), which is used for wound healing, can effectively control both the local and the systemic response. This study was conducted on 24 adult, clinically healthy male rabbits for this purpose. On each animal's back, full-thickness excisional wounds measuring 2 cm x 2 cm were created following sterile skin preparation. The animals were randomly split into two equal groups, each with twelve rabbits. In the group that acts as a control; 5 milliliters of phosphate-buffered saline was used to treat wounds. In the group treated; for the first seven days, the wounds were only treated with (LLLT) at a rate of 5/5 second at 8j/cm2. At the seventh, fourteenth, and 35th days of healing, histopathological biopsies were performed. The control group's histopathology revealed hemorrhage with inflammatory cell infiltration, primarily neutrophils, and congested blood vessels in the gap seven days after surgery. Necrotized neutrophils, hemolysis, and granulation tissue under the dermis were present in the gap at fourteen days. Between the muscle fibers, there was hemolysis. At 35 days, there was irregular proliferation of fibrous connective tissue, and congested blood vessels with mononuclear cell infiltration could be seen in the gap. At seven days, the treated group has completely sloughed the epidermis and a thin crust on the skin's surface with a small incision. In the dermis, there is a lot of infiltration of inflammatory cells, mostly lymphocytes and macrophages. There is also a lot of granulation tissue and a lot of adipose tissue with a lot of thick collagen network. At fourteen days, the epidermis' epithelial layers have healed completely and a keratinized layer is present. In the dermis, a proliferating and thick collagen network, scattered inflammatory cells, and regular fibrosis with hemorrhage and the development of a new B.V. At day 35, look for narrow scar tissue with complete epithelization, a keratinized layer above the epidermis, new vascularization with a lot of regular fibrosis and few regular collagen, new hair follicles, new blood vessels, and scattered macrophages. We concluded that full-thickness wound healing is positively influenced by the use of low level laser therapy (LLLT), which creates a microenvironment favorable to cell growth and differentiation.

Corneal changes after fulguration and cross-linking in experiment

BACKGROUND: Severe progressive forms of infectious keratitis are often associated with the risk of violation of the structural integrity of the eyeball and the development of endophthalmitis. In the presence of negative dynamics against the background of conservative etiotropic therapy for severe keratitis, it is advisable to use surgical methods of treatment. The combination of two surgical methods of influencing a pharmacoresistant infectious process in the cornea — cross-linking and fulguration — is promising and requires further investigation.&#x0D; AIM: In the experiment, to evaluate the effect on the corneal tissue of various modes of direct current fulguration, as well as in combination with cross-linking as well.&#x0D; MATERIALS AND METHODS: An in vivo experimental study was carried out on 19 rabbits (38 eyes) of the Soviet Chinchilla breed, the average body weight of the animals was 2.5–4.0 kg. Depending on the stage of the study, the type and power of exposure during fulguration, the rabbits were divided into 3 groups.&#x0D; RESULTS: When the cornea was exposed to fulguration in mode 5, the changes covered only 10–15 % of the anterior stroma, about 50 μm, and both clinically and histologically were not sufficient. When exposed to mode 6 and 7 after 3 months, changes in the stromal structure extended by about 150 µm. When using mode 8, there was a slight proliferation of connective tissue between the Descemet’s membrane and the endothelium. The combination of cross-linking with fulguration made it possible to obtain a more compact structure of the anterior layers of the corneal stroma and stability of the epithelium.&#x0D; CONCLUSIONS: Fulguration may be a relatively safe treatment for the cornea in pharmacoresistant progressive keratitis. Fulguration and corneal cross-linking can potentiate each other’s effect. Fulguration mode 7 (1.5 W) is optimal at corneal exposition for the eradication of infectious agents.

Case Report: Anatomic Pathology of Bali Cattle Liver Infested with Fasciola gigantica

Infectious diseases pose a significant threat to livestock health and productivity, particularly in developing countries. Fasciolosis, caused by infestation of Fasciola sp., is one such disease of concern. This case report focuses on the anatomic pathologic changes observed in the liver of Bali cattle infested with Fasciola gigantica. The cattle involved in this study were Bali cattle slaughtered at the Mambal Slaughterhouse in Badung, Bali, Indonesia between December 2021. During the specified period, 2 out of the 16 slaughtered cattles tested positive for Fasciola gigantica, representing an infection rate of 12.5%. The primary objective of composing this article is to disseminate information pertaining to the anatomical and pathological alterations observed in Bali cattle as a consequence of fasciolosis. Regarding the observation, the liver exhibited hepatomegaly, characterized by enlarged size and blunt edges, and adult flukes were found in the bile ducts. The surface of the liver parenchyma displayed proliferation of connective tissue, and there was evidence of enlarged portal lymph nodes. Based on these findings, it can be concluded that the Bali cattle in this case report were afflicted with fasciolosis.