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Scorpion venom peptides: Novel therapeutic approaches for inflammatory and hepatic disorders.

Chronic hepatic disorders, such as metabolic dysfunction associated steatohepatitis (MASH), alcohol associated liver disease (ALD), and viral hepatitis (Hepatitis B virus [HBV]/Hepatitis C virus [HCV]), are primarily driven by persistent immune-mediated inflammation and hepatic stellate cell activation leading to fibrosis, yet conventional therapies lack tissue and molecular specificity. Scorpion venom peptides, refined through evolutionary selection, provide highly potent, target specific scaffolds capable of modulating intrahepatic inflammatory networks. Recent in vivo preclinical studies indicate that voltage gated potassium (Kv1.3) channel blocking peptides, such as BmKK2, significantly reduce macrophage activation and inhibit downstream cytokine production, effectively ameliorating diet-induced steatohepatitis and tissue scarring in murine models. Engineered hepatotropic candidates, such as Smp76 and Mucroporin-M1, demonstrate dual therapeutic functions: they neutralize extracellular Hepatitis C particles and suppress key host transcription factors necessary for Hepatitis B replication. This review systematically examines scorpion venom peptides organized by disease category, covering their historical development, structural classification into disulfide-bridged and non-disulfide-bridged families, ion channel specificity, hepatic anti-inflammatory and antiviral mechanisms, and translational challenges including nano-formulation delivery strategies and computational drug design. These target-specific peptides are ultimately positioned as promising molecular leads that may bridge targeted immunomodulation with the resolution of chronic, progressive liver injury.

Anti-inflammatory effects

Distribution of intimal smooth muscle cell masses and their relationship to early atherosclerosis in the abdominal aortas of young swine.

In the abdominal aortas of young mash-fed swine, intimal cell masses (pads, cushions) are located predominantly away from blood vessel orifices. They are found scattered throughout the aorta but nevertheless have a definite pattern of distribution. In the distal one half of the abdominal aorta, they are more frequent in the ventral quandrant than in the dorsal or either lateral quadrant. In the proximal half, intimal cell masses are more frequent in the dorsal quadrant. When experimental atherosclerosis is induced in the abdominal aortas of young swine by either a hypercholesterolemic diet or by aortic ballooning followed by a hypercholesterolemic diet, the distribution of early lesions is similar. The lesions are found predominantly in quadrants where intimal cell masses were found to be most frequent in the control group of swine. The results suggest that most of the lesions, though not necessarily all, arose from pre-existing intimal cell masses beneath the aortic surface.

Animals

Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity, and amphetamine anorexia in the rat.

Bilateral 6-hydroxydopamine lesions of the nucleus accumbens septi (NAS) and olfactory tubercle (OT) caused enhanced intake of wet mash in 23-hr-food-deprived rats tested in photocell activity cages during restricted 30-min sessions. This mild hyperphagia was accompanied by a significant hypoactivity in the group with NAS/OT lesions. No hyperphagia was observed during a prolonged 120-min test session or in free-feeding tests conducted in the home cage. Anorexia induced by d-amphetamine (.5 and 1.5 mg/kg) was unaltered by the lesion, although the locomotor stimulant action of the drug was attenuated. A second experiment showed that the NAS/OT lesion also enhanced food intake in the photocell cages during 30-min sessions with dry food pellets but that food-associated drinking was concomitantly reduced. The results are consistent with the hypothesis that the behavioral changes caused by mesolimbic neuron destruction result in part from an inability to switch from one behavioral activity to another.

Anorexia

Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.

Hepatocellular carcinoma (HCC) is an increasingly prevalent and deadly disease that is initiated by different etiological factors, such as alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis, and other hepatotoxic and hepatocarcinogenic agents. The tumor microenvironment (TME) of HCC is characterized by several different fibroblastic and immune cell types, all of which affect the initiation, progression and metastasis of this malignant cancer. This complex immune TME can be divided into an innate component that includes macrophages, neutrophils, dendritic cells, myeloid-derived suppressor cells, mucosal-associated invariant T cells, natural killer cells, natural killer T cells, and innate lymphoid cells, as well as an adaptive component that includes CD4+ T cells, CD8+ T cells, regulatory T cells, and B cells. In this review, we discuss the latest findings shedding light on the direct or indirect roles of these immune cells (and fibroblastic-like cells such as hepatic stellate cells) in the pathogenesis of HCC. Henceforth, further characterization of this heterogeneous TME is highly important for studying the progression of HCC and developing novel immunotherapeutic treatment options. In line with this, we also review novel groundbreaking experimental techniques and animal models aimed at specifically elucidating this complex TME and discuss emerging immune-based therapeutic strategies intended to treat HCC and predict the efficacy of these immunotherapies.

Humans

Comparative genomics reveals population structure and functional differentiation in Limosilactobacillus fermentum.

Limosilactobacillus fermentum is a widely distributed lactic acid bacterium frequently detected in fermented foods and host-associated microbiota, yet its global genomic diversity and functional variability remain insufficiently characterized. Here, we performed a large-scale comparative genomic analysis of 336 high-quality L. fermentum genomes curated from public databases. Species identity was validated using average nucleotide identity (ANI), and population structure was examined using pairwise ANI comparisons together with Mash-based phylogenetic reconstruction. Clustering at ≥ 99% ANI resolved the dataset into 15 genomic clusters, with four dominant lineages comprising the majority of genomes. Pangenome reconstruction identified 5,853 gene clusters, including 1,325 core genes (22.6%) and a large accessory component dominated by low-frequency genes. Heap's law modeling (λ = 0.19) indicated a weakly open pangenome, suggesting ongoing gene acquisition as additional genomes are sampled. Functional annotation revealed that core genes were primarily associated with essential cellular processes, whereas accessory genes were enriched in carbohydrate metabolism, membrane-associated functions, and defense-related systems. Variation in carbohydrate-active enzymes (CAZymes), transport systems, and stress-response genes was observed across lineages, indicating strain-level functional diversity. Although genomes from human and food sources were broadly distributed across phylogenetic lineages, multivariate analysis showed that gene-content variation was more strongly associated with genomic lineage than with isolation source. These results provide a population genomic framework for understanding genomic diversity and functional potential in L. fermentum.

Phylogeny

The effect of meal feeding and of sham-feeding on insulin secretion in dogs.

After feeding intact conscious dogs 1000 g mashed meat, peripheral venous immunoreactive insulin activity (IRI) increases before any enhancement of amino nitrogen concentration. This course of IRI is paralleled by a decrease of free fatty acids. Meal feeding in dogs, whose pancreatic juice is completely diverted from the gut by a fistula, is followed by a similar IRI increase without a distinct enhancement of amino nitrogen. In oesophagus fistula dogs, sham-feeding meat in 9 out of 15 experiments results in a considerable early IRI increase which is correlated with a small but a significant decrease of blood glucose and free fatty acid concentrations. In these tests there was no amino nitrogen alteration either.

Amino Acids

Toxicity of Crotalaria Goreensis for chickens.

Ground Crotalaria goreensis seed fed to day-old cockerel chickens at 3 different rates in a commercial ration of chick starter mash depressed growth rates. Moist faeces were common. Lesions consistently found included ulceration of the proximal large intestine and a dark grey discolouration of the glandular portion of the proventriculus. C. goreensis should be excluded from all poultry rations.

Animal Feed

Loss of Mtarc1 Protects Against Steatotic Liver Disease in Mice.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) spans from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and can progress to cirrhosis or hepatocellular carcinoma. Despite its prevalence, effective therapies are lacking. Recent genome-wide association studies identified a common missense variant (rs2642438) in the Mitochondrial Amidoxime Reducing Component 1 (MTARC1) gene that protects against liver cirrhosis without increasing cardiovascular disease risk. Biochemical and disease risk signatures associated with carriers of this missense variant also aligned with those of a known loss-of-function MTARC1 variant, suggesting mARC1 inhibition as a potential MASLD treatment. METHODS: To validate mARC1 loss-of-function as protective against MASLD, we generated Mtarc1 knockout (KO) mice and placed them on a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Effects of Mtarc1 KO on obesity and type 2 diabetes were explored using a high-fat diet. Hepatocytes from Mtarc1 KO mice were isolated to explore the molecular mechanisms by which Mtarc1 KO impacts lipid metabolism. RESULTS: Mtarc1 KO mice exhibited no vital growth or development defects. With a high-fat diet-induced obesity model, obese Mtarc1 KO mice exhibited reduced liver mass and lower cholesterol levels, with no effect on glucose homeostasis. In a CDAHFD-induced MASLD model, mARC1 deficiency significantly reduced liver steatosis, profibrosis, and inflammation. Untargeted metabolomics profiling further showed hepatic enrichment of phospholipids in Mtarc1 KO mice. Primary hepatocytes isolated from Mtarc1 KO mice exhibited reduced lipid droplet accumulation, decreased fatty acid uptake, and increased lipid secretion. CONCLUSIONS: These findings support mARC1 inhibition as a promising therapeutic strategy for MASLD/MASH.

Animals

Killer toxin for sake yeast: properties and effects of adenosine 5'-diphosphate and calcium ion on killing action.

The killer character of strain isolated from the main mash of sake brewing which produces a killer substance for sake yeast was transmitted to hybrids of the strain and a standard strain of Saccharomyces cerevisiae through a cytoplasmic determinant. The character was eliminated at 41 degrees C by incubation followed by growth at 30 degrees C. The killer strain produced the killer toxin in a growth-associated manner. A preparation of crude killer toxin extract showed first-order inactivation and a linear Arrhenius plot between 25 and 40 degrees C, with an activation of energy of 55.0 kcal/mol. Addition of 1% of synthetic polymer protected the toxin from inactivation by agitation but not by heat. Enhancement of the killer action toward sensitive yeast cells by only the nucleotide adenosine 5'-diphosphate (ADP) was observed after plating on agar medium as well as after incubation in liquid medium. The addition of CaCl2 reversed the enhancing effect of ADP on killing activity. This action of CaCl2 was inhibited by cycloheximide, suggesting that protein synthesis is required for recovery of toxin-induced cells in the presence of CaCl2. Further, CaCl2 overcame the decrease in the intracellular level of adenosine 5'-triphosphate (ATP) enhanced by ADP in killer-treated cells and also inhibited leakage of ATP from the cells with immediate response. The mode of killing action is discussed in terms of a transient state of the cells and the action of ADP and CaCl2.

Adenosine Diphosphate

Effect of pelleting on the vitamin K activity of various vitamin K3 preparations in chicks.

A study with chicks was conducted to compare the relative vitamin K3 stability of various menadione preparations in mash and pellets. The preparations assayed were menadione sodium bisulfite, menadione sodium bisulfite complex, menadione dimethylpyrimidinol bisulfite and Kastab (a physically stabilized preparation of menadione sodium bisulfite). Pelleting increased the stability of all preparations when measured by the partial thromboplastin assay. The general trend in stability obtained by both procedures was in decreasing order: Kastab, menadione dimethylpyrimidinol bisulfite, menadione bisulfite complex and menadione bisulfite. Stability, determined chemically in vitamin microelement premixes, gave similar results.

Animal Feed

AI-driven diagnostic and prognostic models for metabolic dysfunction-associated steatotic liver disease: insights from clinical, imaging, and multi-omics studies-a scoping review.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most common chronic liver disease around the world, affecting 33.6% of the adult population (95% CI: 28.1%-39.5%; I 2 = 99.9%), or roughly one in three. The extent of the liver damage is variable, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), cirrhosis and hepatocellular carcinoma (HCC). Early diagnosis is essential to prevent serious liver damage. Traditional diagnostic techniques such as liver biopsy, imaging, and biomarker testing are all invasive, costly, reduced sensitive to early-stage disease, and they also have variability among observers. Modern diagnostic and prognostic approaches based on the principles of Artificial Intelligence (AI) and specifically on machine learning (ML) and deep learning (DL) have enabled multimodal approaches integrating clinical, imaging and molecular data. This scoping review conducted per PRISMA-ScR guidelines, synthesizes findings from 73 studies (search window 2020-2026) across three dimensions: clinical data driven models, imaging-based classifiers (ultrasound, CT and MRI), and multi-omics (genomics, transcriptomics and proteomics) techniques. Moreover, emergence of models such as U-Net and LiverNet 2.x, classification models like DeepLiverNet and BiLSTM models, as well as transformer frameworks and the identification of biomarkers models are also described. This study also investigates challenges such as data heterogeneity, data interpretability, fairness and real-world clinical application. Finally, important areas of research opportunities and future directions are highlighted to present a developing clinically applicable, explainable and ethical AI solutions to manage MASLD.

MASLD

[Partial traumatic epiphysiodesis of the lower end of the tibia in children. Treatment with disepiphysiodesis].

The author has treated 20 cases of secondary varus deformity of the tibia after ankle traumas in children. These deformities were related to a partial premature epiphyseal closure, the plate being mashed at the time of the trauma. These cases were usually treated by corrective osteotomy. In two cases an attempt was made at resecting the bone briding the plate and filling the defect by methyl-metacrylate. The results appeared to be encouraging.

Ankle

Liquid chromatography with fluorescence detection of lasalocid sodium in feeds and premixes.

Lasalocid sodium is extracted directly from feeds and premixes with the mobile phase solution, an aliquot is chromatographed, and the concentration (peak height) of lasalocid sodium is measured by high pressure liquid chromatography with fluorescence detection. Chromatography and detection are completed in about 7 min. The results agree well with those found by the official AOAC fluorometric method, 42.A08--42.A13. The method offers an alternative to the AOAC method and has the capability of processing almost twice as many samples. The average recovery of 4 levels (0.0008, 0.0040, 0.0080, and 0.0120%) of lasalocid sodium from feeds is 100%. Replicate assays of typical poultry mashes and pellets containing about 0.0080% lasalocid sodium yielded coefficients of variation of 2.68--3.35%.

Animal Feed

Robenidine resistance in Eimeria tenella.

Robenidine protected chickens against cecal coccidiosis infections initiated by a strain of the parasite that had no previous exposure to drugs. No cross resistance was found with 13 strains resistant to other anticoccidials. A strain of Eimeria tenella that was serially propagated in chickens fed mash containing robenidine became resistant to the chemical. No cross resistance was detected when this experimental strain was tested against 12 other anticoccidials.

Animals

The mechanism of insulin secretion after oral glucose administration. VIII. Pancreatic juice insulin excretion after glucose loading and meal ingestion in normal and vagotomized dogs.

On pancreatic fistula dogs, in the pancreatic juice, immunoreactive insulin has been identified. Insulin excretion is shown to be inhibited by an intravenous glucose load and to be stimulated in a biphasic manner by an oral glucose load or by ingestion of mashed meat. Insulin excretion is reduced 2 months after bilateral truncular vagotomy and the reaction to both oral stimuli is abolished. -- There is no statistical correlation between pancreatic juice insulin and blood glucose, plasma IRI, or plasma amino nitrogen concentrations. Single extrainsular B-cells shown by histologic examination are suggested to be the source of pancreatic juice insulin. Compared to insulin secreted into the portal blood flow, insulin in the pancreatic juice amounts to only 0.1--0.2% of the daily secretory rate of the islets of Langerhans.

Administration, Oral

Collaborative study of assay method for erythromycin in pelleted feeds containing binding agents.

A modified method for analysis of erythromycin in feeds containing the pelleting adjuvants bentonite and Masonex has been evaluated by collaborative study. Erythromycin is freed from the binding action of these adjuvants by an aqueous methanolic pH 8 buffer presoak before extraction with methylal. The recovery values for mash and pellets of 6 different sample types range from 86.6 to 103.0% of theory with a grand mean of 96.8%. This modification has been adopted as official first action.

Animal Feed

Recognizing the allergic person.

Recognition of the allergic individual is facilitated by an awareness of certain characteristic actions and various facial lesions which may be clues to other allergic problems. A gaping expression, clearing of the throat and rubbing or mashing of the eyes and nose may indicate significant rhinitis. Dark circles and bags under the eyes, long, silky eyelashes and injected conjunctivas are other signs. Bruxism and malocclusion may also be related to an allergic diathesis.

Adolescent