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This experiment aimed to study the effects on liver tissue structure and immune performance of grass carp Ctenopharyngodon idellus when the common reed Phragmites australis is in its diet, instead of wheat Triticum aestivum L. Seventy-two healthy grass carps (145.52 ± 2.56 g) were randomly divided into three groups according to their body weight. Fishes in each group were fed an essential diet with 0% (control group), 50% and 100% (test group) common reed, instead of wheat, respectively. After feeding for 41 days, the changes of serum biochemical indices, liver tissue structure and immune related indices of grass carp were detected. The results showed that, compared with the control group, the activities of serum alanine transaminase (ALT) and aspartate transaminase (AST) in the substitution groups were significantly increased (p < 0.05), but still at a normal level. The contents of total protein, albumin and globulin did not change significantly (p > 0.05). Compared with the control group, the liver cells of grass carp in the substitution groups had clear boundaries, tight arrangement and less vacuolation. The contents of serum interleukin-1 (IL-1) and complement 3 (C3) in the 100% substitution group were significantly higher than those in the control group (p < 0.05), and the contents of liver IL-1 and total complement (CH50) in the 100% substitution group were significantly higher than those in the control group (p < 0.05). The contents of IL-1, C3 in serum and IL-1, CH50 in liver in the 50% substitution group were significantly higher than those in the control group (p < 0.05). The mRNA relative expression levels of C3, IL-1, MHC-I and interferon (IFN) in the head-kidney, kidney, liver and spleen of grass carp were significantly affected by feeding the grass carp with different common reed substitution ratios (p < 0.05). In summary, common reed, instead of wheat, in feed can improve the liver tissue structure, and increase the non-specific immune response level, of grass carp. [ABSTRACT FROM AUTHOR]

Phospholipase A2s (PLA2) is a major component of snake venom with diverse pathologic toxicities and, therefore, a potential target for antivenom therapy. Varespladib was initially designed as an inhibitor of mammal PLA2s, and was recently repurposed to a broad-spectrum inhibitor of PLA2 in snake venom. To evaluate the protective abilities of varespladib to hemorrhage, myonecrosis, and systemic toxicities that are inflicted by different crude snake venoms, subcutaneous ecchymosis, muscle damage, and biochemical variation in serum enzymes derived from the envenomed mice were determined, respectively. Varespladib treatment showed a significant inhibitory effect to snake venom PLA2, which was estimated by IC50 in vitro and ED50 in vivo. In animal models, the severely hemorrhagic toxicity of D. acutus and A. halys venom was almost fully inhibited after administration of varespladib. Moreover, signs of edema in gastrocnemius muscle were remarkably attenuated by administration of varespladib, with a reduced loss of myonecrosis and desmin. Serum levels of creatine kinase, lactate dehydrogenase isoenzyme 1, aspartate transaminase, and alanine transaminase were down-regulated after treatment with varespladib, which indicated the protection to viscera injury. In conclusion, varespladib may be a potential first-line drug candidate in snakebite envenomation first aid or clinical therapy. [ABSTRACT FROM AUTHOR]

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. Reference 1 Wang Y., Zhang J., Zhang D., Xiao H., Xiong S., Huang C. Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. The authors would like to correct an error in the original publication [[1]]. [Extracted from the article]

Primary liver cancer is one of the leading causes for cancer-related death worldwide. Transforming growth factor beta (TGF-β) is a pleiotropic cytokine that signals through membrane receptors and intracellular Smad proteins, which enter the nucleus upon receptor activation and act as transcription factors. TGF-β inhibits liver tumorigenesis in the early stage by inducing cytostasis and apoptosis, but promotes malignant progression in more advanced stages by enhancing cancer cell survival, EMT, migration, invasion and finally metastasis. Understanding the molecular mechanisms underpinning the multi-faceted roles of TGF-β in liver cancer has become a persistent pursuit during the last two decades. Contextual regulation fine-tunes the robustness, duration and plasticity of TGF-β signaling, yielding versatile albeit specific responses. This involves multiple feedback and feed-forward regulatory loops and also the interplay between Smad signaling and non-Smad pathways. This review summarizes the known regulatory mechanisms of TGF-β signaling in liver cancer, and how they channel, skew and even switch the actions of TGF-β during cancer progression. [ABSTRACT FROM AUTHOR]

Snake venom is a complex cocktail of toxins which induces a series of clinical and pathophysiological manifestations in victims, including severe local tissue damage and systemic alterations. Deinagkistrodon acutus (D. acutus) ranks among the “big four” life-threatening venomous species in China, whose venom possesses strong myotoxicity and hematotoxicity that often lead to permanent disability or muscle atrophy. Varespladib, an inhibitor of mammalian phospholipase A2 (PLA2), has been recently reproposed as an effective antidote against snakebite envenomation. The present study aimed at evaluating the protective role of varespladib on muscle regeneration in envenomed mice. Mice were grouped and subjected to inoculation with D. acutus venom or a mixture of venom and varespladib or control vehicle in the gastrocnemius muscle. Local injuries including hemorrhage, myonecrosis, ulceration, and systemic damages including general dysfunction, visceral failure, and inflammatory responses were observed at 1, 3, 7, 14, and 21 days. The results indicated that most of the muscle myonecrosis and hemorrhage were alleviated by varespladib. Besides, the pretreated mice recovered rapidly with lesser atrophy and muscle fibrosis. In conclusion, the findings of the present study suggested that varespladib is an effective antidote that could neutralize D. acutus venom and allow for earlier and improved rehabilitation outcome. [ABSTRACT FROM AUTHOR]