Proliferation Of Connective Tissue Research Articles

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.

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.

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

AbstractHyperhomocysteinemia (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 B6 and vitamin B12 folic acid (vitamin B9). Causes of HHcy include deficiency of vitamins B6, B9, and B12, 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 B6, and vitamin B12 lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B6, vitamin B12, 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.

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

AbstractHyperhomocysteinemia (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 B6 and vitamin B12 folic acid (vitamin B9). Causes of HHcy include deficiency of vitamins B6, B9, and B12, 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 B6, and vitamin B12 lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B6, vitamin B12, 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.

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.

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.

Results of Morphological Studies of Various Forms of Chronic Tonsillitis

Traditionally, the diagnosis of chronic tonsillitis is based on the assessment of clinical signs. It should also be born in mind that the morphological examination of the tonsils is an invasive method and can only be used to confirm the diagnosis after tonsillectomy, and not as a routine examination of patients with chronic tonsillitis. Morphological changes in palatine tonsils during chronic tonsillitis are represented by the proliferation of connective tissue in the thickness of the lymphoid tissue, the presence of necrotic foci, damage to the walls of capillary vessels, and disturbances in the crypt epithelium. In the case of the toxic-allergic form of chronic tonsillitis, the process of inflammation in the palatine tonsils proceeds more actively than in the simple form of chronic tonsillitis. However, these changes are not specific. Morphological changes are usually verified by examining the tissue of the tonsils their removal.

Current Symptoms and Pathological Changes of Bursa Fabricius from Commercial Farming Broilers Led to Infectious Bursal Disease

Infectious Bursal Disease (IBD) or Gumboro is caused by the IBD virus of the Birnaviridae family. The disease is acute and highly contagious in young birds. The virus infection causes severe damage to the lymphoid organs i.e. bursa Fabricius leading to immunosuppression. The disease morbidity may reach 100%, while the mortality varies from 20 to 100%, causing high economic losses. Infectious Bursal Disease has remained significant threat although vaccination has been applied. This study aimed to determine the current typical pathological changes in the bursa Fabricius of commercial broilers showing IBD symptoms. The samples were obtained from commercial broiler farms in Sragen, Wonogiri, Batang, and Sleman. Gross lesion examination showed enlargement of the bursa Fabricius with gelatinous material on the serosal surface, oedema with fluid accumulation in the lumen, hemorrhages of the serosal surface, atrophy, and caseous exudate in the lumen. Histopathologic changes of acute IBD include hemorrhages, congestion, lymphocyte necrosis, accumulation of fibrin, oedematous and heterophils infiltration in the interfollicular tissues. Microscopic changes in chronic IBD (5-7 days post infection IBDV) including follicular atrophy, lymphocyte necrosis, vacuolization of the follicle, and proliferation of fibroblast and connective tissue in the interfollicular space. In conclusion, the notable pathological change description of bursa Fabricius in suspected acute is gross lesion (swelling and edema, thickened and enlarged plica bursa Fabricius, hemorraghe), microscopic lesion (congestion, hemorraghe, heterophil infiltration) or chronically IBD infection in broiler chicken was gross lesion (atrophy bursa Fabricius, atrophy and excudate casouse in the lumen bursa Fabricius), microscopic lesion (lymphocyte necrosis, vacuolization of bursa Fabricius follicles, proliferation of fibroblasts and interfollicular connective tissue).

Advances in the Study of Pathological Histology and Pathogenesis of Endometrial Polyps

Endometrial polyps (EPs) are common gynecological diseases among women of childbearing age. They are formed by the proliferation of blood vessels and connective tissue in a portion of the endometrium, resulting in the formation of a polyp-like mass that protrudes into the uterine cavity and varies in size and number. Typically, the body of the uterus is the site of implantation of these polyp-like growths, which are attached to the medial wall of the uterine cavity by a long, thin tip. Irregular vaginal bleeding is the first clinical manifestation of endometrial polyps, and it can often lead to infertility. Studies have shown that the prevalence of endometrial polyps in the female population is approximately 25.0%. With the widespread use of hysteroscopic techniques in clinical practice, knowledge and diagnosis of endometrial polyps have significantly improved. However, pathological examination remains the “gold standard” for final diagnosis in clinical practice. This article aims to review the epidemiology, pathological histology, and pathogenesis of endometrial polyps to reveal their mechanisms and characteristics more accurately and guide further clinical research and treatment. The relevant progress in recent years in this field, both domestically and internationally, is reviewed below.

Possible mechanisms of phlebitis-like abnormal reaction (PLAR) after cyanoacrylate obliteration of varicose veins

Based on their own research and a review of the literature, the authors analyze the possible cellular mechanisms of the development of an inflammatory reaction after the obliteration of varicose veins with cyanoarylate adhesive compounds (CAO), which received the name phlebitis- Like abnormal Reaction (PLAR) in foreign sources. Despite the existing opinion about the “abnormal” nature of the inflammatory reaction, it is noted that the main stages of its development are fully consistent with the currently known molecular and cellular mechanisms of the response of biological tissues to contact with a foreign antigenic substance and are of a natural nature. The cause of the development of acute alterative inflammation in the vein wall is the direct contact of the endothelium with an aggressive environment, which is cyanoacrylate. A specific feature of the development of chronic inflammation in the vein wall is its productive interdaily character, which is replaced by proliferative processes. The main role in the development of successive stages of PLAR development is played by monocytic, mast and giant cells of foreign bodies, as well as the mechanisms underlying the regulation of the functional activity of these cells. During the period of cyanoacrylate biodegradation, its cellular environment corresponds to all morphological features of a phagocytoma, whose activity decreases with the biodegradation of cyanoacrylate with simultaneous connective tissue proliferation. The development of possible chronic granulomatous inflammation is based on a local autoimmune process associated with the formation of giant multinucleated epithelioid cells (Langerhans cells). In conclusion, it is emphasized that today, when using various cyanoacrylate compounds for the purpose of adhesive obliteration of veins, taking into account the accumulated clinical data and morphological studies, the final answers to the existing reasonable objections about the complete safety of the use of cyanoacrylates in clinical practice should be given by fundamental immunohistochemical and genetic studies.

Mammary fibromatosis in a female dog: case report

Fibromatosis, or desmoid tumour, is characterized by excessive and infiltrative proliferation of connective tissue originating from aponeurotic muscle structures. Mammary fibromatosis is rare in humans and animals and its precise aetiology is unknown. A 10-year-old mixed-breed female dog developed a mass in the right cranial thoracic mammary gland (M1) and underwent lumpectomy. The mass was firm, with an irregular surface and distinct limits. Microscopically, it was a neoplastic proliferation of fusiform cells with low atypia, interspersed with abundant dense collagenous tissue, confirmed by histochemical staining with Gomori's trichrome and Masson's trichrome and immunopositivity for vimentin and smooth muscle actin, confirming mammary fibromatosis. Mammary fibromatosis in dogs needs further studies to elucidate its clinical, epidemiological and aetiopathogenic aspects.

The Upregulation of the FBLN1 and HS3ST4 Genes May Represent a Potential Mechanism Driving the Fibrotic Progression in Primary Myelofibrosis and Leading to Adverse Prognosis

Myelofibrosis is a group of diseases characterized by increased proliferation of bone marrow fibrous connective tissue and a decrease in hematopoietic cells, leading to impaired bone marrow hematopoietic function. Myelofibrosis includes primary myelofibrosis（PMF）, myelofibrosis secondary to polycythemia vera（post-PV MF）, and myelofibrosis secondary to essential thrombocythemia（post-ET MF）. Studies suggest that certain genes may be responsible for driving the development of myelofibrosis and causing adverse prognosis. By conducting RNA-Seq analysis, we investigated the differentially expressed genes and their impact on prognosis in primary myelofibrosis and secondary myelofibrosis. Furthermore, we analyzed the potential mechanisms driving the progression of fibrosis. Additionally, we performed a comparative analysis of the clinical features among various types of myelofibrosis. In this study, we performed transcriptome sequencing to analyze gene expression differences in 14 overt-PMF samples, 5 post-ET MF samples, and 3 post-PV MF samples.Functional and pathway analyses were conducted on these differentially expressed genes, and cluster heatmaps were used to visualize their expression patterns.Simultaneously, we performed a comparative analysis of clinical characteristics among 370 overt-PMF patients, 96 post-ET MF patients, and 52 post-PV MF patients.The study revealed that compared to post-PV MF, overt-PMF showed 81 upregulated and 2 downregulated differentially expressed genes, while compared to post-ET MF, overt-PMF displayed 19 upregulated and 3 downregulated differentially expressed genes (Figure a) (Figure b). Based on the similarity of gene expression profiles among the samples, a clustering analysis was performed (Figure c).The results demonstrated that in overt-PMF, the FBLN1 gene was significantly upregulated compared to post-PV MF and was enriched in pathways related to extracellular matrix formation and cell adhesion among the differentially expressed genes (Figure d). Additionally, the HS3ST4 gene was significantly upregulated in overt-PMF compared to post-ET MF and was enriched in pathways related to interleukin-8 generation and regulation of cytokine production involved in inflammatory responses.In the analysis of clinical characteristics among different types of myelofibrosis patients, it was observed that overt-PMF was more prone to transform into acute leukemia compared to post-PV MF, had a higher tendency to develop transfusion dependency (Figure e), and exhibited lower hemoglobin levels and hematocrit at the time of diagnosis (Figure f). Moreover, compared to post-ET MF, overt-PMF had a higher likelihood of transforming into acute leukemia and lower platelet counts at the time of diagnosis. The research findings indicate that the expressions of FBLN1 and HS3ST4 genes are significantly upregulated in overt-PMF, and patients with overt-PMF have a worse prognosis compared to those with post-PV MF and post-ET MF. Previous studies have shown that FBLN1 is involved in extracellular matrix assembly, promoting the formation and stabilization of collagen fibers. It can also interact with integrin receptors and other cell adhesion molecules, participating in cell-extracellular matrix signaling processes. On the other hand, HS3ST4 is involved in processes such as cell adhesion, cell migration, and cell signaling. Based on these findings, it is speculated that the upregulation of FBLN1 and HS3ST4 gene expressions may potentially drive the progression of fibrosis and lead to an adverse prognosis in patients with myelofibrosis. Acknowledgement: This research was funded by the Key R&amp;D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; Zhejiang Medical Association Clinical Medical Research special fund project, No. 2022ZYC-D09. Correspondence to: Dr Jian Huang, Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine. No. 79 Qingchun Road. Hangzhou, Zhejiang, PR China. househuang@zju.edu.cn

COMPREHENSIVE ASSESSMENT OF MORPHOLOGICAL CHANGES IN THE LIVER OF RABBITS EXPOSED TO WATER-SOLUBLE SILICON FOR THREE MONTHS

The article presents the results obtained when studying the liver of rabbits who were in an experiment with the intake of silicon with drinking water at a concentration of 20 mg / l expressed in terms of silicon. The aim of the study was a comprehensive assessment of liver changes in laboratory rabbits under the conditions of the experiment with the intake of water-soluble silicon for three months. Material and methods. Rabbits were kept in a vivarium on a standard diet with free access to drinking water for three months. Animals of the control group (n = 3) received bottled drinking water, rabbits of the experimental group (n = 3) received the same water, but with the addition of sodium metasilicate enneahydrate at a concentration of 20 mg /l expressed in terms of silicon. After the animals were removed from the experiment, the liver was extracted. A part of the liver was sent to a cryostat for freezing with further preparation of fresh slices with a thickness of 10 microns and producing a Cross, Evan and Rost reaction to detect histamine luminescent structures, the other part was placed in a 10% formalin solution for subsequent paraffin embedding. Paraffin blocks were made; sections of 5 microns thick after deparaffination were stained with hematoxylin and eosin, methyl green-pyronine by Brachet method, as well as by Van Gieson method to identify connective tissue. The measurement results were considered statistically significant at p &lt; 0.05. Results and their discussion. When stained with hematoxylin and eosin in the liver preparations of rabbits of the experimental group who received silicon with drinking water at a concentration of 20 mg/l ad libitum for three months, statistically significant increases in the average area of hepatocytes, the average area of hepatocyte nuclei, and the average diameter of sinusoidal capillaries were revealed in comparison with the preparations in the control group. An increase in the area of central veins was noted, but these changes were not statistically significant. A change in the shape of hepatocytes' nuclei was observed, which was manifested by a decrease in the shape factor of the nucleus and eccentricity and an increase in the index of the nucleus contour, as well as leukocytic infiltration of the portal tract area, formation of areas of hepatocytes' focal necrosis, proliferation of connective tissue with the formation of portal fibrosis and portoportal septa. In rabbits of the experimental group, a decrease in the DNA optical density was determined in liver histopreparations stained by Brush method in hepatocyte nuclei. We found an increase in the intensity of histamine luminescence in the luminescent granular liver cells of rabbits containing it. Conclusions. The intake of silicon at a concentration of 20 mg/l for three months results in pronounced morphological changes in the liver of rabbits.

Keloid nomogram prediction model based on weighted gene co-expression network analysis and machine learning

Keloids are benign skin tumors resulting from the excessive proliferation of connective tissue in wound skin. Precise prediction of keloid risk in trauma patients and timely early diagnosis are of paramount importance for in-depth keloid management and control of its progression. This study analyzed four keloid datasets in the high-throughput gene expression omnibus (GEO) database, identified diagnostic markers for keloids, and established a nomogram prediction model. Initially, 37 core protein-encoding genes were selected through weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the centrality algorithm of the protein-protein interaction network. Subsequently, two machine learning algorithms including the least absolute shrinkage and selection operator (LASSO) and the support vector machine-recursive feature elimination (SVM-RFE) were used to further screen out four diagnostic markers with the highest predictive power for keloids, which included hepatocyte growth factor (HGF), syndecan-4 (SDC4), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), and Rho family guanosine triphophatase 3 (RND3). Potential biological pathways involved were explored through gene set enrichment analysis (GSEA) of single-gene. Finally, univariate and multivariate logistic regression analyses of diagnostic markers were performed, and a nomogram prediction model was constructed. Internal and external validations revealed that the calibration curve of this model closely approximates the ideal curve, the decision curve is superior to other strategies, and the area under the receiver operating characteristic curve is higher than the control model (with optimal cutoff value of 0.588). This indicates that the model possesses high calibration, clinical benefit rate, and predictive power, and is promising to provide effective early means for clinical diagnosis.