Vimentin , an indispensable protein, is responsible for the formation of intermediate filament structures within cells and plays a crucial role in viral infections

However, the precise role of VIM in classical swine fever virus  infection remains unclear. Herein, we systematically investigated the  function of VIM in CSFV replication. We demonstrated that both knockdown and  overexpression of VIM affected CSFV replication. Furthermore, we observed by  confocal microscopy the rearrangement of cellular VIM into a cage-like structure  during CSFV infection. Three-dimensional imaging indicated that the  cage-like structures were localized in the endoplasmic reticulum and ringed  around the double-stranded RNA , thereby suggesting that VIM was  associated with the formation of the viral replication complex .  Mechanistically, phosphorylation of VIM at serine 72 , regulated by the  RhoA/ROCK signaling pathway, induced VIM rearrangement upon CSFV infection.

 Confocal microscopy and coimmunoprecipitation assays revealed that VIM  colocalized and interacted with CSFV NS5A. Structurally, it was determined that  amino acids 96 to 407 of VIM and amino acids 251 to 416 of NS5A were the  respective important domains for this interaction. Importantly, both VIM  knockdown and disruption of VIM rearrangement inhibited the localization of NS5A  in the ER, implying that VIM rearrangement recruited NS5A to the ER for VRC  formation. Collectively, our results suggest that VIM recruits NS5A to form a  stable VRC that is protected by the cage-like structure formed by VIM  rearrangement, ultimately leading to enhanced virus replication. These findings  highlight the critical role of VIM in the formation and stabilization of VRC,  which provides alternative strategies for the development of antiviral drugs.  IMPORTANCE Classical swine fever , caused by classical swine fever virus  , is a highly infectious disease that poses a significant threat to the  global pig industry. Therefore, gaining insights into the virus and its  interaction with host cells is crucial for developing effective antiviral  measures and controlling the spread of CSF.

Purchase  have shown that CSFV  infection induces rearrangement of the endoplasmic reticulum, leading to the  formation of small vesicular organelles containing nonstructural protein and  double-stranded RNA of CSFV, as well as some host factors. These organelles then  assemble into viral replication complexes . In this study, we have  discovered that VIM recruited CSFV NS5A to form a stable VRC that was protected  by a cage-like structure formed by rearranged VIM. This enhanced viral  replication. Our findings not only shed light on the molecular mechanism of CSFV  replication but also offer new insights into the development of antiviral  strategies for controlling CSFV. Sodium-glucose cotransporter-2 inhibitors are anti-hyperglycemic agents  that prevent glucose reabsorption in proximal tubular cells. SGLT2i improves  renal outcomes in both diabetic and non-diabetic patients, indicating it may have  beneficial effects beyond glycemic control.

Here, we demonstrate that SGLT2i  affects energy metabolism and podocyte lipotoxicity in experimental Alport  syndrome . In vitro, we found that SGLT2 protein was expressed in human and  mouse podocytes to a similar extent of tubular cells. Newly established  immortalized podocytes from Col4a3 knockout mice accumulate lipid  droplets along with increased apoptosis when compared to wildtype podocytes.  Treatment with SGLT2i empagliflozin reduces lipid droplet accumulation and  apoptosis in AS podocytes. Empagliflozin inhibits the utilization of  glucose/pyruvate as a metabolic substrate in AS podocytes but not in AS tubular  cells. In vivo, we demonstrate that empagliflozin reduces albuminuria and  prolongs the survival of AS mice. Empagliflozin-treated AS mice show decreased  serum blood urea nitrogen and creatinine levels in association with reduced  triglyceride and cholesterol ester content in kidney cortices when compared to AS  mice.

Lipid accumulation in kidney cortices correlates with the decline in renal  function. In summary, empagliflozin reduces podocyte lipotoxicity and improves  kidney function in experimental AS in association with the energy substrates  switch from glucose to fatty acids in podocytes. interests exist. KS Kumar Sharma, is founder of SygnaMap.. SM Sandra Merscher, is  an inventor on pending or issued patents  aimed at preventing and treating renal disease.  They stand to gain royalties from their future commercialization.

SM holds  indirect equity interest in, and potential royalty from, ZyVersa Therapeutics,  Inc. by virtue of assignment and licensure of a patent estate. SM is supported by  Aurinia Pharmaceuticals Inc.. AF Alessia Fornoni, is an inventor on pending  or issued patents aimed at preventing and treating renal disease. They stand to gain  royalties from their future commercialization. AF is Vice-President of L&F  Health LLC and is a consultant for ZyVersa Therapeutics, Inc.

ZyVersa  Therapeutics, Inc has licensed worldwide rights to develop and commercialize  hydroxypropyl-beta-cyclodextrin from L&F Research for the treatment of kidney  disease. AF also holds equities in Renal 3 River Corporation. AF and SM are  supported by Aurinia Pharmaceuticals Inc..