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Structurel Insights to the Conversation regarding Filovirus Glycoproteins with all the Endosomal Receptor Niemann-Pick C1: A Computational Study.
Triple-negative breast cancer (TNBC) is heterogeneous cancer with poor prognosis among the other breast tumors. Rapid recurrence and increased progression rate could be reasons for the poor prognosis of this type of breast cancer. Recently, because of the lack of specific targets in multiple cancer treatment, immune checkpoint blockade therapies with targeting PD-1/PD-L1 axis have displayed significant advances and improved survival. Among different types of breast cancers, TNBC is considered more immunogenic with high T-cell and other immune cells infiltration compared to other breast cancer subtypes. This immunogenic characteristic of TNBC is a beneficial marker in the immunotherapy of these tumors. Clinical studies with a focus on immune checkpoint therapy have demonstrated promising results in TNBC treatment. In this review, we summarize clinical trials with the immunotherapy-based treatment of different cancers and also discuss the interaction between infiltrating immune cells and breast tumor microenvironment. In addition, we focus on the signaling pathway that controls PD-L1 expression and continues with CAR T-cell therapy and siRNA as novel strategies and potential tools in targeted therapy.
1) Characterize the progression of exercise intolerance in monocrotaline-induced pulmonary hypertension (PH) in mice and 2) evaluate the therapeutic effect of aerobic exercise training (AET) on counteracting skeletal and cardiac dysfunction in PH.

Wild type C57BL6/J mice were studied in two different time points 2months and 4months. Exercise tolerance was evaluated by graded treadmill exercise test. The AET was performed in the last month of treatment of 4months' time point. Cardiac function was evaluated by echocardiography. Skeletal muscle cross-sectional area was assessed by immunofluorescence. The diameter of cardiomyocytes and pulmonary edema were quantified by staining with hematoxylin-eosin. The variables were compared among the groups by two-way ANOVA or non-paired Student's t-test. Significance level was set at p<0.05.

After 2months of MCT treatment, mice presented pulmonary edema, right cardiac dysfunction and left ventricle hypertrophy. After 4months of MCT treatment, mice showed pulmonary edema, right and left cardiac dysfunction and remodeling associated with exercise intolerance and skeletal muscle atrophy. AET was able to reverse cardiac left ventricle dysfunction and remodeling, prevent exercise intolerance and skeletal muscle dysfunction. Thus, our data provide evidence of skeletal muscle abnormalities on advanced PH. AET was efficient in inducing an anti-cardiac remodeling effect besides preventing exercise intolerance.

Our study provides a robust model of PH in mice, as well as highlights the importance of AET as a preventive strategy for exercise intolerance and, skeletal and cardiac muscle abnormalities in PH.
Our study provides a robust model of PH in mice, as well as highlights the importance of AET as a preventive strategy for exercise intolerance and, skeletal and cardiac muscle abnormalities in PH.Traditional methods for cancer therapy, including radiotherapy, chemotherapy, and immunotherapy are characterized by inherent limitations. Bacteria-mediated tumor therapy is becoming a promising approach in cancer treatment due to the ability of obligate or facultative anaerobic microorganisms to penetrate and proliferate in hypoxic regions of tumors. It is widely known that anaerobic bacteria cause the regression of tumors and inhibition of metastasis through a variety of mechanisms, including toxin production, anaerobic lifestyle and synergy with anti-cancer drugs. These features have the potential to be used as a supplement to conventional cancer treatment. To the best of our knowledge, no reports have been published regarding the most common tumor-targeting bacterial agents with special consideration of obligate anaerobes (such as Clostridium sp., Bifidobacterium sp.) and facultative anaerobes (including Salmonella sp., Listeria monocytogenes, Lactobacillus sp., Escherichia coli, Corynebacterium diphtheriae and Pseudomonas sp). In this review, we summarize the latest literature on the role of these bacteria in cancer treatment.
Probiotics and their metabolites (SCFA) can regulate energy homeostasis. read more The present study thus evaluates the synergistic effect of probiotic Enterococcus faecalis AG5 on HFD induced obesity and the role of propionic acid (PA) in apoptosis induction of 3T3-L1 pre-adipocyte.

Male Wistar rats (n=24) were used to develop an HFD induced obesity model for 24weeks. The effect of the orally administered probiotic AG5 (18th-24th weeks, 1×10
CFU/ml) was evaluated using physiological, biochemical, anthropometry, histopathological and serological analyses. Apoptosis in 3T3-L1 pre-adipocyte was assessed using flow cytometry, protein expression of PPARγ, 5-LOX, NF-κB, p-AKT, caspase 10 and detection of caspase 3/7 by Immunofluorescence confirmed the apoptosis induced by PA.

Probiotic AG5 significantly reduced body weight, BMI, serum cholesterol, triglycerides (p<0.05) and improved HDL, insulin and leptin but lowered LDL and VLDL (p>0.05). An inflammatory response was reduced as evident by TNF-α IHC. AG5 reduced adipocyte hypertrophy and fatty acid accumulation. Flow cytometry confirmed late apoptosis in PA-AG5 and standard PA treated 3T3-L1 cells. 5-LOX inhibition is associated with apoptosis induction, and increased caspase 1p 10 is related to cell death initiation. The study initially showed a low PPARγ activity inhibiting 5-LOX which may relate to adipose apoptosis. Finally caspase 3/7 detection using immunofluorescence proved the role of PA in adipocyte apoptosis.

The present study is a novel approach towards obesity mitigation involving adipocyte apoptosis. The role of SCFA in adipocyte apoptosis is very limited which can prove to be novel therapeutic approach in the future.
The present study is a novel approach towards obesity mitigation involving adipocyte apoptosis. The role of SCFA in adipocyte apoptosis is very limited which can prove to be novel therapeutic approach in the future.
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