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Context.--The histologic features in patients with acute-on-chronic liver failure (ACLF) are evolving, and histologic indicators of patients' poor prognosis are not yet fully established. Objective.--To evaluate the independent histologic predictors of 28-day mortality in ACLF patients on core-needle liver biopsies. Design.--Core-needle biopsies from patients with a diagnosis of ACLF (n = 152) as per the European Association for the Study of the Liver criteria were included during 8 years. Liver biopsies from 98 patients with compensated chronic liver disease were included as disease controls for histologic comparison. Features of ongoing changes, such as hepatic necrosis, hepatic apoptosis, cholestasis, hepatocyte degeneration, bile ductular proliferation, Mallory-Denk bodies, steatosis, and extent of liver fibrosis, were analyzed for predicting short-term mortality (28 days). A P value of Results.--In our cohort of ACLF patients, the following etiologies for acute decompensation were identified: alcohol, 47 of 152 (30.9%); sepsis, 24 of 152 (15.7%); hepatotropic viruses, 20 of 152 (13.1%); drug-induced liver injury, 11 of 152 (7.2%); autoimmune flare, 9 of 152 (5.9%); mixed etiologies, 5 of 152 (3.2%); and cryptogenic, 36 of 152 (23.6%). On histologic examination, hepatic necrosis (P Conclusions.--Dense lobular necroinflammatory activity is a clinically independent histologic predictor of 28-day short-term mortality in patients with ACLF., Acute-on-chronic liver failure (ACLF) syndrome is characterized by abrupt hepatic decompensation secondary to acute insult in patients with chronic liver disease (CLD), having high short-term mortality. (1-3) The diagnosis and [...]

Fibroblast Growth Factors (FGFs) function as signaling molecules within various signaling pathways, regulating the proliferation, migration, and differentiation of soft connective tissues, nerves, epithelial tissue, and bone. The FGF family comprises 22 members, with acidic Fibroblast Growth Factor (aFGF/FGF-1) and basic Fibroblast Growth Factor (bFGF/ FGF-2) being of primary significance. This article explores the biochemical and biological properties of different FGFs, elucidating their roles in various biological processes. Additionally, it delves into the interactions between FGFs and Receptor tyrosine kinases (RTKs), which activate several cell signaling cascades, such as the RAS/MAPK (Mitogen-activated Protein Kinase) pathway, PI3K (phosphoinositide 3-kinase)/AKT (v-akt murine thymoma viral oncogene homolog) pathway, PLC-γ (Phospholipase C-γ) pathway, and Signal Transducer and Activator of Transcription (STAT) pathway, to facilitate diverse cellular functions. The article also examines methods for engineering FGFs, including N-terminal truncation, point mutations, or combinations thereof, for therapeutic applications in tissue regeneration, angiogenesis, and repairing damaged tissues such as cartilage, bone, ligaments, and skin. Finally, it concludes with a discussion of the delivery systems for FGFs, encompassing scaffolds, hydrogels, as well as nano- and micro-particulate methods. [ABSTRACT FROM AUTHOR]

Poorly differentiated colonic carcinoma with rhabdoid features is a rarely described entity. Our knowledge regarding the molecular phenotype of the tumor is evolving. We herein report a similar tumor with rhabdoid differentiation identified in the splenic flexure, which on histological examination showed a poorly differentiated phenotype with epithelioid to spindled morphology, tumor giant cells, and rhabdoid differentiation. The tumor was mismatch repair-proficient, deficient of INI1/SMARCB1, KRAS mutated (A146×), BRAFV600E mutated (c.1799T > A), and NRAS wild-type, indicating serrated differentiation in the tumor. The patient died after 3.5 months post-surgery. INI1-deficient poorly differentiated carcinoma of the colon is a rare, aggressive colonic malignancy showing a serrated phenotype. Routine identification and subtyping are important keeping in mind the distinct tumor phenotype, resistance to conventional chemotherapy, and dismal prognosis. [ABSTRACT FROM AUTHOR]

Background and aim: Basic differentiation between an inflammatory bowel disease (IBD)-type colitis and a non-IBD type of colitis is the essential histological pre-requisite before further subclassifications are made. The combination of mucosal prominent eosinophilic cell infiltrate along with basal plasmacytosis is supposed to be a useful histological feature that can differentiate between IBD-type and non-IBD-type colitis. Hence, this systematic review and metaanalysis aimed to assess the reliability of mucosal basal plasmacytosis and eosinophilia for histological differentiation of IBD-type versus non-IBD-type colitis. Methods: We searched the PROSPERO, PubMed, Embase, and Scopus from January 1, 2000 to July 30, 2022 for all types of studies (prospective, cross-sectional, or retrospective studies) having histological features (including mucosal basal plasmacytosis, eosinophilia, and neutrophilic infiltration) in IBD and/or non-IBD colitis cases. Two reviewers extracted data, which were aggregated using random-effects models. Results: The 59 selected articles were evaluated for the predecided parameters. Both basal plasmacytosis and lamina propria plasmacytosis did not show any significant correlation between IBD-type and non-IBD-type colitis. The proportions for basal plasmacytosis with 95% CI were 0.50 (0.19-0.82) in IBD-type colitis and 0.46 (0.40-0.52) in non-IBD-type colitis, with a P value of .79. The proportion of lamina propria plasmacytosis with 95% CI was 0.67 (0.42-0.92) in IBD and 0.60 (0.35-0.85) in non-IBD-type colitis, with a P value being .7. Conclusions: This systematic review documented the dearth of published data on key histological features such as basal plasmacytosis and mucosal eosinophilia which are believed to differentiate between IBD-type and non-IBD-type colitis. [ABSTRACT FROM AUTHOR]

Burn induced injuries are commonly encountered in civilian and military settings, leading to severe morbidity and mortality. Objective of this study was to construct microporous bioactive scaffolds of gelatin-hyaluronic acid suffused with aloe-vera gel (Gela/HA/AvG), and to evaluate their efficacy in healing partial-thickness burn wounds. Scaffolds were characterized using Fourier transform-infrared spectroscopy, Scanning electron microscopy, and Thermo-gravimetric analysis to understand intermolecular interactions and morphological characteristics. In-vitro fluid uptake ability and hemolytic index of test scaffolds were also determined. In-vitro collagenase digestion was done to assess biodegradability of scaffolds. Wound retraction studies were carried out in Sprague Dawley rats inflicted with partial-thickness burn wounds to assess and compare efficacy of optimized scaffolds with respect to negative and positive control groups. In-vivo gamma scintigraphy using Technetium-99m labeled Immunoglobulin-G ( 99m Tc- IgG) as imaging agent was also performed to validate efficacy results. Histological and immunohistochemical comparison between groups was also made. Scaffolds exhibited mircoporous structure, with pore size getting reduced from 41.3 ± 4.3 µm to 30.49 ± 5.7 µm when gelatin conc. was varied from 1% to 5%. Optimized test scaffolds showed sustained in-vitro swelling behavior, were biodegradable and showed hemolytic index in range of 2.4–4.3%. Wound retraction study along with in-vivo gamma scintigraphy indicated that Gela/HA/AvG scaffolds were not only able to reduce local inflammation faster but also accelerated dermis regeneration. Immunohistochemical analysis, in terms of expression levels of epidermal growth factor and fibroblast growth factor-2 also corroborated in-vivo efficacy findings. Gela/HA/AvG scaffolds, therefore, can potentially be developed into an effective dermal regeneration template for partial-thickness burn wounds. [ABSTRACT FROM AUTHOR]

Alcohol is the most abused psychoactive substance and known hepatotoxicant. Present study elucidates possible therapeutic effect of oral alpha-ketoglutarate (AKG) supplementation against alcohol induced hepatic dysfunction, using biochemical, histopathological and most importantly, in vivo functional imaging approaches. Animals were divided into three groups of 6 animals each. Group-I (control): Normal saline; Group-II: 20% (v/v) solution of ethanol (5 ml/day) intragastrically using oral gavage for 2 months. Group-III: ethanol treatment as in group-II along with AKG supplementation (2g/kg/bw; intragastrically using oral gavage for 2 months). In vivo hepatobiliary scintigraphy was performed in all animals using 99mTc-mebrofenin (99mTc-MEB) as radiotracer to determine changes in (a) Hepatic extraction fraction (HEF), for quantification of radiotracer uptake, (b) Time to reach maximum hepatic uptake (Tpeak), and (c) Time for hepatic uptake to reduce by 50% (T1/2peak). Biochemical (alanine aminotransferase, aspartate aminotransferase, reduced glutathione, superoxide dismutase, catalase, and lipid peroxidation) and histological parameters were also studied. Hepatic uptake and excretion kinetics using 99mTc-MEB scintigraphy showed prompt 99mTc-MEB clearance from liver in control group (HEF: 91.26 ± 2.32; Tpeak: 143 ± 23 sec; T1/2peak: 434 ± 41 sec), while it was significantly abnormal in ethanol group and showed less efficient radiotracer accumulation (HEF: 62.72 ± 5.6; Tpeak: 201 ± 33 sec; T1/2peak: 542 ± 52 sec). Supplementation of AKG along with ethanol significantly improved liver function (HEF: 76.42 ± 5.3; Tpeak: 155 ± 34 sec; T1/2peak: 455 ± 22 sec). Biochemical and histopathology parameters were correlative to findings of functional imaging study. Results strongly indicate hepatoprotective potential of AKG against alcohol-induced hepatic injury. Study further proposes the use of in vivo hepatobiliary scintigraphy for high throughput screening of other hepatoprotectants. [ABSTRACT FROM AUTHOR]

Objective: Alpha-ketoglutarate (α-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP) induced toxicity in rats. Materials and Methods: Animals were divided into three groups of six animals each. Group I (Vehicle control): Normal Saline, Group II (APAP): A single intraperitoneal injection of 0.6 g/kg, Group III (APAP + α-KG): APAP as in Group II with α-KG treatment at a dose of 2 g/kg, orally for 5 days. Then the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) with oxidative stress markers including malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and histopathology were analyzed. Results: The results indicate that APAP caused significant elevations in ALT, AST, ALP, and MDA levels, while GSH, SOD, and CAT were significantly depleted while co-administration of α-KG showed a significant (P < 0.05) reduction in the severity of these damages. Histologically, the liver showed inflammation and necrosis after APAP treatment, which were significantly restored with co-administration of α-KG. Conclusion: These results indicate the possible therapeutic potential of α-KG in protecting liver damage by APAP in rats. [ABSTRACT FROM AUTHOR]