Interlobular Ducts Research Articles

A novel immunofluorescence study of Lingual Salivary Glands in the Egyptian Tortoise (Testudo kleinmanni) and its ecological significance

The Egyptian tortoise (Testudo kleinmanni) is remarkably adapted to its harsh desert environment, a characteristic that is crucial for its survival under extreme conditions. This study was aimed at providing a deeper understanding of the lingual salivary gland structures in the Egyptian tortoise and examining how these structures help the tortoise manage hydration and nutrition in arid conditions. Utilizing a combination of light microscopy and immunofluorescence, this research introduced pioneering methods involving seven different antibodies, marking a first in the study of reptilian salivary glands. Our investigations categorized the tortoise’s salivary glands into papillary and non-papillary types. The papillary glands were further classified into superficial, deep, interpapillary, and intraepithelial salivary glands, while non-papillary glands included superficial and deep lingual types. Structurally, these glands are organized into lobules, delineated by interlobular septa, and are equipped with a duct system comprising interlobular, intercalated, and main excretory ducts with gland openings on the tongue's surface and the papillae surfaces. Notably, the superficial glands displayed both tubuloalveolar and acinar configurations, whereas the deep lingual glands were exclusively acinar. Immunofluorescence results indicated that α-smooth muscle actin (α-SMA) was prevalent in myoepithelial cells, myofibroblasts, and blood vessels, suggesting their integral role in glandular function and support. E-cadherin was predominantly found in epithelial cells, enhancing cell adhesion and integrity, which are critical for efficient saliva secretion. Importantly, Mucin 1 (MUC1) and Mucin 5B (MUC5B) staining revealed that most glands were mucous in nature, with MUC5B specifically marking mucin within secretory cells, confirming their primary function in mucous secretion. PDGFRα and CD34 highlighted the presence of telocytes and stromal cells within the glandular and interlobular septa, indicating a role in structural organization and possibly in regenerative processes. Cytokeratin 14 expression was noted in the basal cells of the glands, underscoring its role in upholding the structural foundation of the epithelial barrier. In conclusion, this detailed morphological and immunological characterization of the Egyptian tortoise’s salivary glands provides new insights into their complex structure and essential functions. These findings not only enhance our understanding of reptilian physiology but also underline the critical nature of salivary glands in supporting life in arid environments. This study's innovative use of a broad range of immunofluorescence markers opens new avenues for further research into the adaptive mechanisms of reptiles.

Alteration of Sublingual Gland after Exposure to 6-Mercaptopurine in Male Rat: Potential Efficacy of Propolis

Objective: Chemotherapeutic drugs not only have a therapeutic effect, but also cause serious damage to healthy organs. In this study, we investigated on the possible efficacy of propolis (PS) on the sublingual gland tissues exposed to 6-mercaptopurine (6MR) in male rats. Materials and Methods: Twenty-eight Wistar albino rats were allocated to four groups: control (KON), PS, 6MR, 6MR+PS. At 12 days of trial, sublingual glands of all rats were immediately dissected and analysed using the stereological technique and histological examination. Results: Our findings revealed a significant increase in the total volume of stroma and significant decrease in the total volume of the total volumes of mucous acini, straited ducts, interlobular ducts, and intralobular ducts in the 6MR group than the KON group (p<0.05). A significant decrease was also found in the mucous cell number and the serous cell number in the 6MR group than the KON group (p<0.05). In the 6MR+PS group, we observed that the total volume of stroma, as well as the mucous cell number and the serous cell number were increased compared to the 6MR group (p<0.05). Besides, the total volumes of mucous acini, straited ducts, interlobular ducts, and intralobular ducts were significantly increased in the 6MR+PS group than the 6MR group (p<0.05). Conclusion: Our results showed that 6MR treatment caused toxicity in sublingual gland tissues, as well as PS application improved such changes in sublingual glands exposed to 6MR.

Morphological examination of the visual system and orbital region in the red panda (Ailurus fulgens fulgens)

ObjectivesThe red panda is currently the only surviving member of the Ailuridae family in the Caniformia suborder. In this study, we provide data on anatomical, morphometric, histological and histochemical examination of the orbital region, eyelids, orbital gland, and eye tunics in two adult males Ailurus fulgens fulgens from the Wroclaw Zoological Garden, Poland.MethodsThe study involved morphometric analysis of the eyeball and selected accessory organs of the eye, along with analysis of the bony orbit, including its morphometry, macroscopic, and microscopic evaluation. Microscopic evaluation encompassed histological and histochemical staining, with the former involving hematoxylin & eosin (H&E), Movat pentachrome, picro-Mallory trichrome, Fontana-Masson, and the latter including PAS, AB pH 1.0, AB pH 2.5; AB pH 2.5/PAS, and HDI.ResultsThe upper (UE) and lower (LE) eyelids presented well-developed tarsal glands, sebaceous glands, and a characteristic simple alveolar gland (producing a mucous secretion). The palpebral part of the lacrimal gland was present. A single lymphoid follicle was observed only in the upper eyelids. The superficial gland of the third eyelid (SGTE) was a multilobar acinar complex that produces mucous secretion and is contained within the interlobular ducts of numerous aggregates of lymph nodes. The third eyelid (TE) was T-shaped and composed of hyaline tissue, containing CALT. The lacrimal gland (LG) also revealed a multilobar acinar complex that produced mucous secretion, with a single lymphoid follicle. The cornea consisted of 4 layers, as Bowman’s membrane was absent. The Vogt palisades composed of 7–10 layers of epithelial cells were demonstrated. The pupil was horizontally ovoid at rest (post-mortem). The sphincter pupil and the dilator pupil were well developed. Macroscopically, the tapetum lucidum appeared as a milky, non-opalescent crescent. Histologically, the choroidal tapetum lucidum cellulosum consisted of 5 to 9 layers of loosely packed oval cells. The retina showed a composition similar to that of terrestrial nocturnal carnivores.ConclusionsThe results of our research indicate that the anatomical features of the eye and orbital region in the red panda share similarities with those described in the Musteloidea clade, as well as the Canidae and Ursidae families.

Distribution of TRPC3 and TRPC6 in the human exocrine and endocrine pancreas

BackgroundExpression and function of TRPC3 and TRPC6 in the pancreas is a controversial topic. Investigation in human tissue is seldom. We aimed to provide here a detailed description of the distribution of TRPC3 and TRPC6 in the human exocrine and endocrine pancreas. MethodsWe collected healthy samples from cadavers (n = 4) and visceral surgery (n = 4) to investigate the respective expression profiles using immunohistochemical tracing with knockout-validated antibodies. ResultsTRPC3- and TRPC6-proteins were detected in different pancreatic structures including acinar cells, as well as epithelial ductal cells from intercalate, intralobular, and interlobular ducts. Respective connective tissue layers appeared unstained. Endocrine islets of Langerhans were clearly and homogenously immunolabeled by the anti-TRPC3 and anti-TRPC6 antibodies. Insular α, β, γ, and δ cells were conclusively stained, although no secure differentiation of cell types was performed. ConclusionsDue to aforementioned antibody specificity verification, protein expression in the immunolabeled localizations can be accepted. Our study in human tissue supports previous investigations especially with respect to acinar and insular α and β cells, while other localizations are here reported for the first time to express TRPC3 and TRPC6, ultimately warranting further research.

МОРФОЛОГИЧЕСКИЕ ИЗМЕНЕНИЯ В ПЕЧЕНИ ПРИ МУКОВИСЦИДОЗЕ У ДЕТЕЙ

Background. Cystic fibrosis (CF) is an autosomal recessive disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, characterized by damage to vital organs, a severe course and an unfavorable outcome. Liver cirrhosis is a relatively rare manifestation of cystic fibrosis. Objective. To study the causes of death, hepatic morphological changes in CF according to autopsy data and to present a description of a case of CF with rapidly progressing liver cirrhosis in a 6-year-old child. Material and methods. An analysis of clinical, laboratory and instrumental studies of CF and the results of hepatic morphological changes was carried out according to the data of 10 autopsies performed at the State Healthcare Institution "GRCPB". Results. Among the 10 patients died from a mixed form of CF, there were 5 patients aged 1-3 months, 2 patients aged 1.5 years, 1 patient aged 4.5 years, 1 patient aged 6 years and 1 patient was 19 years old. Infant patients had predominant intestinal damage with the development of intestinal obstruction and peritonitis, older age groups had lung damage with the development of chronic pulmonary heart disease, chronic pulmonary heart failure, and to a lesser extent - pathology of the pancreas and gastrointestinal tract. In one 6-year-old patient, CF was complicated by diabetes mellitus as well as liver cirrhosis with portal hypertension. All patients had severe protein-energy deficiency, psychosomatic and psychopathological symptoms. The results of pathohistological examination of the liver of infant patients showed dilation of the interlobular bile ducts with cholestasis and periductal fibrosis. The severity of these liver changes increased gradually alongside with patients’ age, including the progression of fatty degeneration. In a number of cases, diffuse fibrosis was recorded, resulting in liver cirrhosis with portal hypertension. At autopsy, the extrahepatic bile ducts and gallbladder were dilated and filled with bile of a viscous consistency. Conclusions. The nature of hepatic morphological changes in CF depends on the age of the patients and on the influence of exogenous factors. Only timely diagnosis and early complex therapy for CF will reduce the progression of irreversible processes in various organs and prolong the life of patients.

Clinicopathological features of Sjogren's syndrome complicated with liver injury

Objective: To study the clinicopathological features of Sjogren's syndrome (SS) with liver injury and to improve the understanding of this disease. Methods: Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson's trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted. Results: The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group (P=0.006) and NALFD group (P=0.011) were significantly higher than those in other groups (P<0.05). Conclusions: The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.

Differential expression of various isoforms of superoxide dismutase in the cells of the human exocrine pancreas.

Superoxide dismutase (SOD) is an enzyme that plays acrucial role in protecting cells from oxidative damage. Our study aims to address the lack of papers simultaneously analyzing the immunoreactivity of all three distinct isoforms of SOD in human exocrine pancreas cells. Superoxide dismutases (SODs) facilitate the conversion of superoxide radicals into less harmful substances. By neutralizing superoxide radicals, SODs help prevent the formation of highly reactive and destructive species that can adversely affect manifold cellular components. The study analyzed immunoreactivity of SODs in samples of six healthy adult human pancreases, while using the indirect immunohistochemical method under alight microscope. SOD1 was predominantly found in centroacinar cells and epithelial cells of the duct system while SOD2 was mainly detected in the epithelial cells of interlobular ducts. Both enzymes were prominently present in the basal region of acinar cells near the cell nucleus. The expression of SOD3 was observed to be rare. Understanding the intracellular metabolism of SODs in healthy exocrine pancreas cells serves as abasis for determining the precise role of oxidative damage and SOD signaling in the pathogenesis of various pancreatic diseases, including chronic pancreatitis and pancreatic cancer (Fig. 6, Ref. 24). Text in PDF www.elis.sk Keywords: antioxidants, histology, immunohistochemistry, pancreas, superoxide dismutase.

High neutrophil-lymphocyte ratio indicates a worse response to ursodeoxycholic acid in primary biliary cholangitis: a retrospective cohort study

BackgroundPrimary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by inflammation of the interlobular bile ducts. Ursodeoxycholic acid (UDCA) is the only FDA approved first-line therapy for PBC, but up to 40% of patients with PBC have an incomplete response to UDCA. Neutrophil-to-lymphocyte (NLR) has been used to predict prognosis in various liver diseases. There is limited evidence on the treatment response to UDCA in PBC patients. Our study aimed to evaluate the relationship between NRL and the response to UDCA treatment in PBC patients.MethodsA total of 257 primary biliary cholangitis (PBC) patients treated with UDCA (13–15 mg/kg/d) were enrolled in this retrospective study. The response to treatment was evaluated based on alkaline phosphatase levels ≤1.67 times the upper limit of the normal value after 12 months of UDCA treatment. Multivariable logistic regression analysis was performed to investigate the association between NLR at baseline and the response to 12 months of UDCA treatment after adjusting for important confounding variables. The stability of the results was evaluated by unadjusted and adjusted models.ResultsThe results of multiple regression analysis showed that NLR at baseline was positively associated with the nonresponse to UDCA treatment after adjustments for potential confounders (age, sex, BMI, hypertension, arterial plaque, thyroid disease, jaundice, albumin, globulin, total bile acid, ALP, GGT, LDLC, total cholesterol, hemoglobin, and APTT) (OR = 1.370, 95% CI 1.066–1.761). These results reveal that NLR is an independent risk factor for UDCA treatment nonresponse.ConclusionsOur results suggest that PBC patients with a high NLR had a worse response to UDCA therapy.

Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis

BackgroundPrimary biliary cholangitis is a rare, chronic cholestatic liver disease characterized by the destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. Whether elafibranor, an oral, dual peroxisome proliferator-activated receptor (PPAR) α and δ agonist, may have benefit as a treatment for primary biliary cholangitis is unknown.MethodsIn this multinational, phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients with primary biliary cholangitis who had had an inadequate response to or unacceptable side effects with ursodeoxycholic acid to receive once-daily elafibranor, at a dose of 80 mg, or placebo. The primary end point was a biochemical response (defined as an alkaline phosphatase level of <1.67 times the upper limit of the normal range, with a reduction of ≥15% from baseline, and normal total bilirubin levels) at week 52. Key secondary end points were normalization of the alkaline phosphatase level at week 52 and a change in pruritus intensity from baseline through week 52 and through week 24, as measured on the Worst Itch Numeric Rating Scale (WI-NRS; scores range from 0 [no itch] to 10 [worst itch imaginable]).ResultsA total of 161 patients underwent randomization. A biochemical response (the primary end point) was observed in 51% of the patients (55 of 108) who received elafibranor and in 4% (2 of 53) who received placebo, for a difference of 47 percentage points (95% confidence interval [CI], 32 to 57; P<0.001). The alkaline phosphatase level normalized in 15% of the patients in the elafibranor group and in none of the patients in the placebo group at week 52 (difference, 15 percentage points; 95% CI, 6 to 23; P=0.002). Among patients who had moderate-to-severe pruritus (44 patients in the elafibranor group and 22 in the placebo group), the least-squares mean change from baseline through week 52 on the WI-NRS did not differ significantly between the groups (−1.93 vs. −1.15; difference, −0.78; 95% CI, −1.99 to 0.42; P=0.20). Adverse events that occurred more frequently with elafibranor than with placebo included abdominal pain, diarrhea, nausea, and vomiting.ConclusionsTreatment with elafibranor resulted in significantly greater improvements in relevant biochemical indicators of cholestasis than placebo. (Funded by GENFIT and Ipsen; ELATIVE ClinicalTrials.gov number, NCT04526665.)

Histological Study of Exocrine Portion of Pancreas in Guinea fowl (Numida meleagris)

The histological structure of the exocrine pancreas was examined in the current study for fifteen healthy adult female Laying hens. The study showed the pancreas was serous tubuloacinar gland, which has both an exocrine and an endocrine component, the parenchyma of the gland was encircled by a thin layer of loose connective tissue capsule. The exocrine part formed of acini (secretory unites) and excretory ducts. In the current study, the shape of the acini were ovoid, rounded or elongated, were lined by a single layer of pyramidal to columnar cells. The duct system started from centroacinar cells and was organized as intercalated ducts, intra lobular ducts, inter lobular ducts, and main pancreatic ducts. The intercalated ducts were lined by single layer of simple squamous, intra lobular ducts was encircled by simple cuboidal cells, interlobular ducts was lined with simple columnar epithelium and the main ducts were lined with simple columnar epithelial cells. The pancreas of Laying hens was identical to other bird species, but with a few minor species.&#x0D;

Cellular and Molecular Mechanisms of Toxic Liver Fibrosis in Rats Depending on the Stages of Its Development.

Liver fibrogenesis in male Wistar rats was induced with the thioacetamide solution by introducing into the stomach with a probe at a dose of 200 mg/kg of animal body weight 2 times per week. The process dynamics was studied at 5 time points (control, week 3, week 5, week 7, and week 9). The mRNA levels of tweak, fn14, ang, vegfa, cxcl12, and mmp-9 genes in liver were detected by real-time polymerase chain reaction. Immunohistochemical study was performed on paraffin sections. The CD31, CD34, CK19, α-SMA, FAP, CD68, CD206, CX3CR1, and CD45 cells were used as markers. Fibrosis degree was determined in histological sections, stained in line with the Mallory technique, according to the Ishak's semi-quantitative scale. Two simultaneously existing morphologically heterogeneous populations of myofibroblasts expressing different types of markers (FAP, α-SMA) were identified in rat liver. Prior to the onset of transformation of fibrosis into cirrhosis (F1-F4, weeks 3-7), FAP+ and SMA+ cells were localized in different places on histological specimens. All stages of liver fibrosis development were accompanied by an increase in the number (p=0.0000), a change in the phenotypic structure and functional properties of macrophages. The CK19+ cells of the portal areas differentiated into cholangiocytes that formed interlobular bile ducts and ductules, as well as hepatocytes that formed rudiments of new hepatic microlobules. Pathological venous angiogenesis and heterogeneity of endotheliocytes of the intrahepatic vascular bed were detected. Two options for changes in mRNA expression of the selected genes were identified. The level of the fn14 and mmp-9 mRNAs at all stages of fibrosis was higher (p=0.0000) than in control rats. For tweak, ang, vegfa, and cxcl12 mRNAs, the situation was the opposite - the level of genes decreased (p=0.0000). There were strong and moderate correlations between the studied target genes (p<0.05). It was established that the stages of toxic fibrosis had morphological and molecular genetic features. The FAP+ cells make the main contribution to development of portal and initial stage of bridging fibrosis. The stellate macrophages and infiltrating monocytes/ macrophages can potentially be used for development of new therapeutic strategies for liver pathology treatment. One should take into account the features of the markers' expression by endothelial cells during the study of the intrahepatic vascular bed. Joint study of genes is a necessary ad-hoc parameter in fundamental and preclinical research.

THE MORPHOLOGICAL AND FUNCTIONAL ASSESSMENT OF FAP+ AND α-SMA+-CELLS IN DIFFERENT TIMES OF RAT TOXIC LIVER FIBROSIS

Qualitative study of the source of the fibro-genic cell population in relation to the etiology and stage of fibrosis, as well as an understanding of the molecular mechanisms that regulate changes in the phenotype of hepatic fibroblasts, are of paramount importance in the development of pharmacological drugs. The purpose of the study was a morphological and functional assessment of activated portal fibroblasts (FAP+) and fat-accumulating cells (α-SMA+) of the liver at various stages of toxic liver fibrosis in rats. Liver fibrosis and cirrhosis in male Wistar rats were induced with thioacetamide solution for 17 weeks. Morphological examination of the liver was carried out on paraffin sections stained with hematoxylin and eosin using the Mallory method; immunohistochemical examination was carried out using polyclonal rabbit antibodies to the portal fibroblast antigen FAP and using monoclonal mouse antibodies to the α-SMA+ cell antigen. Before the onset of liver fibrosis stage F3/F4, from weeks 3 to 7, the number of FAP+ and α-SMA+ cells increased alternately. During the stages of transformation of fibrosis into cirrhosis from 7 to 11 weeks, their number increased slightly. At the stage of incomplete (F5) and before the onset of significant cirrhosis (F6) from weeks 11 to 15, the number of FAP+ and α-SMA+ cells were inconsistent and there was an alternating increase and decrease in their number. α-SMA+ cells before the start of the process of transformation of fibrosis into cirrhosis (F4/F5) were observed in sinusoids and foci of necrosis. Then they were detected both in sinusoids and in connective tissue trabeculae. FAP+ cells at the stage of portal fibrosis (F1) were localized near the interlobular vessels and interlobular bile ducts of the portal zones, and from the F2/F3 period they were detected in connective tissue trabeculae and sinusoids. In quantitative terms, α-SMA+ cells predominated at all stages of fibrosis. Based on the results obtained, it can be assumed that FAP+ cells make a major contribution to the development of the portal and initial stages of bridging fibrosis. They should be considered as one of the myofibroblast populations in thioacetamide-induced liver fibrogenesis.

Hepatic graft-versus-host disease: what we know, when to biopsy, and how to diagnose

Graft-versus-host disease (GVHD) is one of the serious complications that may develop after hematopoietic cell transplantation (HCT), for hematologic malignancies, solid organ transplantation, and other hematologic disorders. GVHD develops due to T lymphocytes present in the graft attacking the host antigens, which results in tissue damage. A significant number of HCT patients develop acute or chronic GVHD, which may affect multiple organs including the liver. The diagnosis of hepatic GVHD (hGVHD) is challenging as many other conditions in HCT patients may lead to liver dysfunction. Particularly challenging among the various conditions that give rise to liver dysfunction is differentiating sinusoidal obstruction syndromeand drug-induced liver injury (DILI) from hGVHD on clinical grounds and laboratory tests. Despite the minimal risks involved in performing a liver biopsy, the information gleaned from the histopathologic changes may help in the management of these very complex patients. There is a spectrum of histologic features found in hGVHD, and most involve histopathologic changes affecting the interlobular bile ducts. These include nuclear and cytoplasmic abnormalities including dysmorphic bile ducts, apoptosis, and cholangiocyte necrosis, among others. The hepatitic form of hGVHD typically shows severe acute hepatitis. With chronic hGVHD, there is progressive bile duct loss and eventually fibrosis. Accurate diagnosis of hGVHD is paramount so that timely treatment and management can be initiated. Techniques to prevent and lower the risk of GVHD from developing have recently evolved. If a diagnosis of acute GVHD is made, the first-line of treatment is steroids. Recurrence is common and steroid resistance or dependency is not unusual in this setting. Second-line therapies differ amonginstitutions and have not been uniformly established. The development of GVHD, particularly hGVHD, is associated with increased morbidity and mortality.

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma (2022 version).

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

Sublingual floor of Rahmani sheep (Ovis aries): A scanning electron microscopy and histomorphology analysis.

The current study investigated the sublingual floor of Rahmani sheep (Ovis aries). Samples from nine healthy adult sheep have been analysed using morphometrical, scanning electron microscopic (SEM), and histological examination. The sublingual floor of the sheep was formed of a rostral prefrenular part (spatula-shaped) and two lateral sublingual recesses. Right and left sublingual caruncles were asymmetrical in length and each one had a serrated border, divided into three papillae. At higher magnifications, the three papillae of the sublingual caruncle's edge were variable in shape, with other two papillae were demonstrated underneath the caruncle. Each sublingual recess had a sublingual fold (plica sublingualis) extended from the level of frenulum linguae till the glossopalatine arch, bordered with caudolaterally directed papillae till the level of first lower molar cheek teeth. The sublingual salivary glands were mixed (seromucoid) type. The glandular lobule consisted of mucous acini and sporadic serous acini, as well as the presence of some mucous acini capped by acidophilic cells, serous demilunes. The mucous acinus was formed of pyramidal mucous cells with pale stained cytoplasm and basally located nuclei. Two ducts; major sublingual and submandibular ducts were observed within the submucosa of the sublingual caruncle. The sublingual ductal pseudostratified columnar epithelium was interspersed by more goblet cells than that of the submandibular duct. Collagen fibres around the glandular lobules, intralobular and interlobular excretory ducts as well as the connective core of the papillae were noticed. By SEM, two epithelium-lined pits on the surface of the sublingual floor mucosa caudal to the central incisive teeth were termed orobasal organ. As the first study to give a comprehensive analysis of the sheeps' sublingual floor, this one serves as a baseline for future clinical studies.

Understanding immune mechanisms to create novel treatments for primary biliary cholangitis

Understanding immune mechanisms to create novel treatments for primary biliary cholangitis Professor Channakeshava S Umeshappa from Dalhousie University discusses the burden of primary biliary cholangitis and how understanding immune mechanisms may help to treat it. Primary biliary cholangitis (PBC) is characterised by chronic inflammation of the interlobular bile ducts, leading to fibrosis, cirrhosis, and liver failure if left untreated. Symptoms of PBC include fatigue, jaundice, itchy skin, abdominal pain, nausea or vomiting, dry eyes and mouth, and bone and joint aches. The incidence of PBC is increasing worldwide,(1) but is most common in Europe and North America.(2) PBC has a female predominance, affecting primarily middle-aged women (over 90% of the PBC cases). Clinically, it is often diagnosed by detecting anti-mitochondrial autoantibodies and elevated alkaline phosphatase enzymes in blood tests.

Primary biliary cholangitis: molecular pathogenesis perspectives and therapeutic potential of natural products.

Primary biliary cirrhosis (PBC) is a chronic cholestatic immune liver disease characterized by persistent cholestasis, interlobular bile duct damage, portal inflammation, liver fibrosis, eventual cirrhosis, and death. Existing clinical and animal studies have made a good progress in bile acid metabolism, intestinal flora disorder inflammatory response, bile duct cell damage, and autoimmune response mechanisms. However, the pathogenesis of PBC has not been clearly elucidated. We focus on the pathological mechanism and new drug research and development of PBC in clinical and laboratory in the recent 20 years, to discuss the latest understanding of the pathological mechanism, treatment options, and drug discovery of PBC. Current clinical treatment mode and symptomatic drug support obviously cannot meet the urgent demand of patients with PBC, especially for the patients who do not respond to the current treatment drugs. New treatment methods are urgently needed. Drug candidates targeting reported targets or signals of PBC are emerging, albeit with some success and some failure. Single-target drugs cannot achieve ideal clinical efficacy. Multitarget drugs are the trend of future research and development of PBC drugs.

A case of primary biliary cholangitis – diagnostic and treatment approaches

Primary biliary cholangitis (PBC) is a chronic, autoimmune, slowly progressive liver disease, characterized by the presence of antimitochondrial antibodies (AMA), cholestatic syndrome, and histological lesions of the interlobular bile ducts, with the potential progression to liver fibrosis and cirrhosis. AMA or AMA-M2 are specific markers for diagnosis of PBC, detected in about 90 % of patients. Antinuclear antibodies (ANA) specific for primary biliary cholangitis, anti-sp100 or anti-gp210 subtypes, can be used as markers of PBC diagnosis in case of patients with negative AMA. In addition to being specific for diagnosis of PBC, the presence of anti-gp210 was associated with more severe forms, rapid progression and poor prognosis of the disease. The first therapeutic option for PBC is considered ursodeoxycholic acid (UDCA), and for patients with a suboptimal response, it is recommended second-line treatment with obeticholic acid. 8-10 % of patients with PBC may have overlap syndrome with autoimmune hepatitis (AIH), which occurs with biochemical, serological and/or histological features of AIH in patients with cholestatic manifestations of PBC. „Paris Criteria” help to identify patients with PBC/AIH overlap syndrome. The article also examines a clinical case of PBC, AMA negative, which required additional investigations for evaluation, diagnostic discussion and current management of overlap syndrome associating PBC and autoimmune hepatitis.

Proliferative Activity of Myoepithelial Cells in Normal and Diabetic Parotid Glands Based on Double Immunostaining Labeling

AIM: This study aimed to examine the effect of diabetes mellitus on the histology of parotid glands and to give a scientific overview of the distribution and the proliferative activity of myoepithelial cells (MECs) encircling both ducts and acini in parotid gland of both normal and diabetic mongrel dogs. MATERIALS AND METHODS: Twelve male mongrel dogs were used in the experiment and divided into two equal groups, group I, control group, group II, dogs with alloxan-induced diabetes. The dogs of the group II were injected by fresh preparation of a single dose of 100 mg/kg body weight of alloxan monohydrate dissolved in physiological saline. Ten days later, blood glucose level was determined using enzymatic colorimetric test; dogs presented a glucose level at or above 200 mg/dL were included in the diabetic group of the experiment. Three months later, dogs were sacrificed and the parotid glands from all groups were dissected and prepared for histological examination and double immunohistochemical expression of both actin and proliferating cell nuclear antigen (PCNA). RESULTS: Histological findings using H and E staining confirmed that the parotid gland parenchyma of the diabetic group had glandular atrophy characterized by loss of normal gland structure, acinar degeneration, and dilatation of the duct system with the presence of duct like structure. Moreover, there was a predominance of the fibrous component with the presence of fat cells within the gland compartments. Immunohistochemical findings of parotid gland of control group revealed positive scattered actin staining of weak to mild quantity in cells embracing some acini and intralobular ducts. Expression of PCNA in actin-positive cells revealed few scattered reactions embracing some acini and small ducts. Parotid gland of diabetic dogs revealed positive actin staining of mild-to-moderate quantity in the cells encircling the acini, intralobular, and some interlobular ducts. Expression of PCNA in actin- positive cells revealed mild-to-moderate positive reaction more concentrated in the cells surrounding both acini and intercalated ducts. CONCLUSION: Routine histological findings of diabetic dogs in our findings showed abundant pathological changes in parenchymal tissue elements, including acinar, ductal, and MECs that had a significant impact on saliva production and secretion resulting in dry mouth. The proliferative activity of MECs in the control group indicated a routine regeneration process, whereas the abundant proliferative activity in the diabetic group might indicate pathological transformation rather than regeneration, especially because no remedial measures were taken during this investigation.

Diagnosis and Treatment of Primary Biliary Cholangitis

Primary biliary cholangitis (PBC) is an autoimmune disease prevalent in middle-aged women and characterized by chronic cholestasis. PBC is diagnosed when at least two of the following three criteria are met: elevated alkaline phosphatase, presence of PBC-specific autoantibodies such as the anti-mitochondrial antibody or PBC-specific anti-nuclear antibodies, and non-suppurative inflammation of the interlobular bile duct after excluding other causes including drugs and biliary obstruction. The first-line treatment for PBC is ursodeoxycholic acid (UDCA, 13-15 mg/kg/day). The response to UDCA is predictive of long-term prognosis and should be evaluated 6-12 months after the UDCA treatment. The second-line treatments for PBC recommended due to an inadequate response to UDCA include obeticholic acid and fibrates. Symptoms and complications, including pruritus, sicca syndrome, and osteoporosis, should be evaluated and appropriately managed.