14 research outputs found
Everolimus is a potent inhibitor of activated hepatic stellate cell functions in vitro and in vivo , while demonstrating anti-angiogenic activities
No full textProgression of liver fibrosis to HCC (hepatocellular carcinoma) is a very complex process which involves several
pathological phenomena, including hepatic stellate cell activation, inflammation, fibrosis and angiogenesis.
Therefore inhibiting multiple pathological processes using a single drug can be an effective choice to curb the
progression of HCC. In the present study, we used the mTOR inhibitor everolimus to observe its effect on the in vitro
activation of hepatic stellate cells and angiogenesis. The results of the present study demonstrated that everolimus
treatment blocked the functions of the immortalized human activated hepatic stellate cell line LX-2 without affecting
the viability and migration of primary human stellate cells. We also observed that treatment with everolimus
(20 nM) inhibited collagen production by activated stellate cells, as well as cell contraction. Everolimus treatment
was also able to attenuate the activation of primary stellate cells to their activated form. Angiogenesis studies
showed that everolimus blocked angiogenesis in a rat aortic ring assay and inhibited the tube formation and
migration of liver sinusoidal endothelial cells. Finally, everolimus treatment reduced the load of tumoral
myofibroblasts in a rat model of HCC. These data suggest that everolimus targets multiple mechanisms, making it a
potent blocker of the progression of HCC from liver fibrosis
Chicken chorioallantoic membrane as a reliable model to evaluate osteosarcoma—an experimental approach using SaOS2 cell line
No full textIn ovo administration of human recombinant leptin shows dose dependent angiogenic effect on chicken chorioallantoic membrane
No full textBACKGROUND: Leptin, the cytokine produced by white adipose tissue is known to regulate food energy homeostasis through its hypothalamic receptor. In vitro studies have demonstrated that leptin plays a major role in angiogenesis through binding to the receptor Ob-R present on ECs by stimulating and initiating new capillary like structures from ECs. Various in vivo studies indicate that leptin has diverse effect on angiogenesis. A few reports have showed that leptin exerts pro angiogenic effects while some suggested that it has antiangiogenic potential. It is theoretically highly important to understand the effect of leptin on angiogenesis to use as a therapeutic molecule in various angiogenesis related pathological conditions. Chicken chorio allantoic membrane (CAM) on 9th day of incubation was incubated with 1, 3 and 5 μg concentration of HRL for 72 h using gelatin sponge. Images where taken after every 24 h of incubation and analysed with Angioguant software. The treated area was observed under microscope and histological evaluation was performed for the same. Tissue thickness was calculated morphometrically from haematoxylin and eosin stained cross sections. Reverse transcriptase PCR and immunohistochemistry were also performed to study the gene and protein level expression of angiogenic molecules. RESULTS: HRL has the ability to induce new vessel formation at the treated area and growth of the newly formed vessels and cellular morphological changes occur in a dose dependent manner. Increase in the tissue thickness at the treated area is suggestive of initiation of new capillary like structures. Elevated mRNA and protein level expression of VEGF165 and MMP2 along with the activation of ECs as demonstrated by the presence of CD34 expression supports the neovascularization potential of HRL. CONCLUSION: Angiogenic potential of HRL depends on the concentration and time of incubation and is involved in the activation of ECs along with the major interaction of VEGF 165 and MMP2. It is also observed that 3 μg of HRL exhibits maximum angiogenic potential at 72 h of incubation. Thus our data suggest that dose dependent angiogenic potential HRL could provide a novel role in angiogenic dependent therapeutics such as ischemia and wound healing conditions
High molecular weight heparin-induced angiogenesis mainly mediated via basic fibroblast growth factor-2- an in-vivo (CAM) and in-silico analysis
No full textBackground: High-molecular weight heparin (HMWH), a molecule extensively used as an anticoagulant, shows concentration-dependent angiogenic and anti-angiogenic potential. So far, no studies have reported the interactive potential of HMWH with various pro-angiogenic growth factors under physiological conditions. Haence, we aimed to find the impact of major pro-angiogenic growth factors under HMWH induced angiogenesis. Methods: Chicken Chorioallantoic Membranes (CAMs) are incubated with various concentrations of HMWH. Semiquantitative PCR method was implemented to measure the changes in the transcription level of pro-angiogenic growth factors. The scanning electron microscopic technique is applied to find the morphological changes in CAM. Molecular docking and molecular dynamics simulation studies using NAMD and CHARMM force field discerned the heparin-binding mode with the pro-angiogenic growth factors. Results: HMWH can enhance the transcription level of major pro-angiogenic growth factors, significantly impacting FGF2 under 100 μM concentration. The in-silico analysis reveals that HMWH shows the highest binding affinity with FGF2. Further, molecular dynamics and interaction studies using 1 kDa Heparin against FGF2 showed that the former binds stably with the latter due to a strong salt bridge formation between the sulfate groups and arginine residues (ARG 119 and ARG109). Conclusion: The combined experimental and in-silico analysis results reveal that HMWH can interact with pro-angiogenic growth factors under micromolar concentration while inducing angiogenesis. This observation further supports the therapeutic benefits of HMWH as an angiogenic factor under such low concentration. This technique is used to replenish the blood supply to chronic wounds to speed healing and prevent unnecessary amputations
Cytological Profile of Solid and Cystic Lesions Arising from Various Sites in the Body: A Cross-sectional Study
No full textIntroduction: Fine Needle Aspiration Cytology (FNAC) is a minimally invasive, cost-effective, and efficient technique for obtaining diagnostic cellular material with minimal discomfort and a low patient complication rate.
Aim: To study various solid and cystic lesions in the body using FNAC, followed by histopathological examination for definitive diagnosis.
Materials and Methods: The present cross-sectional Study was conducted on 383 patients who underwent surgery for cystic and solid lesions in the Department of Pathology at Chengalpattu Medical College, Chengalpattu, Tamil Nadu, India. over a period of one year from June 2022 to June 2023. Patients with various solid lesions (breast, thyroid, salivary gland lesions, lymphoma, etc.) and cystic lesions (epidermal cysts, ganglionic cysts, fibro-cystic breast disease, etc.) referred for cytopathological analysis were included. FNAC results were tabulated, and histopathological examination of surgically removed tissues was performed for definitive diagnosis.
Results: The study shows that FNAC is useful for diagnosing solid and cystic lesions, with a concordance rate of 83.66% for solid lesions and 90.90% for cystic lesions when compared to histopathology. However, it also highlights difficulties in distinguishing between benign and malignant thyroid and breast lesions, emphasising the need for further testing in uncertain cases.
Conclusion: The FNAC is a simple, non traumatic, safe, cost-effective outpatient procedure. It provides high diagnostic accuracy for many conditions related to both solid and cystic lesions, especially when combined with imaging guidance and expert cytological interpretation
Additional file 3 of Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein
No full textAdditional file3: Table S1. Molecular docking results for phyto compounds- from PyRx
An Overview on the Therapeutic Function of Foods Enriched with Plant Sterols in Diabetes Management
No full textDiabetes is one of the most significant health issues across the world. People identified with diabetes are more vulnerable to various infections and are at a greater risk of developing cardiovascular diseases. The plant-based food we consume often contains many sterol-based bioactive compounds. It is well documented that these compounds could effectively manage the processes of insulin metabolism and cholesterol regulation. Insulin resistance followed by hyperglycemia often results in oxidative stress level enhancement and increased reactive oxygen species production. At the molecular level, these changes induce apoptosis in pancreatic cells and hence lead to insulin insufficiency. Studies have proved that plant sterols can lower inflammatory and oxidative stress damage connected with DNA repair mechanisms. The effective forms of phyto compounds are polyphenols, terpenoids, and thiols abundant in vegetables, fruits, nuts, and seeds. The available conventional drug-based therapies for the prevention and management of diabetes are time-consuming, costly, and with life-threatening side effects. Thereby, the therapeutic management of diabetes with plant sterols available in our daily diet is highly welcome as there are no side effects. This review intends to offer an overview of the present scenario of the anti-diabetic compounds from food ingredients towards the therapeutic beneficial against diabetes
Additional file 4 of Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein
No full textAdditional file4: Figure S3. Molecular interaction of TMPRSS2 with phyto compounds obtained from PyRx
Additional file 1 of Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein
No full textAdditional file1: Figure S1. Represents the catalytic site (Pink Colour) and substrate binding site (Blue colour) of TMPRSS2
Additional file 5 of Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein
No full textAdditional file5: Table S2. Molecular docking results for phyto compounds -from Schrodinger
