Browsing by Author "Kumar, Sanjay"

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    Caveolin-1 knockout mitigates breast cancer metastasis to the lungs via integrin α3 dysregulation in 4T1-induced syngeneic breast cancer model
    (Springer Nature, 2024) Singh, Dhirendra Pratap; Pathak, Rashmi; Chintalaramulu, Naveen; Pandit, Abhishek; Kumar, Avinash; Ebenezer, Philip J.; Kumar, Sanjay; Duplooy, Alexander; White, Mary Evelyn; Jambunathan, Nithya; Dharmakumar, Rohan; Francis, Joseph; Radiology and Imaging Sciences, School of Medicine
    Caveolin-1 (Cav-1) is a critical lipid raft protein playing dual roles as both a tumor suppressor and promoter. While its role in tumorigenesis, progression, and metastasis has been recognized, the explicit contribution of Cav-1 to the onset of lung metastasis from primary breast malignancies remains unclear. Here, we present the first evidence that Cav-1 knockout in mammary epithelial cells significantly reduces lung metastasis in syngeneic breast cancer mouse models. In vitro, Cav-1 knockout in 4T1 cells suppressed extracellular vesicle secretion, cellular motility, and MMP secretion compared to controls. Complementing this, in vivo analyses demonstrated a marked reduction in lung metastatic foci in mice injected with Cav-1 knockout 4T1 cells as compared to wild-type cells, which was further corroborated by mRNA profiling of the primary tumor. We identified 21 epithelial cell migration genes exhibiting varied expression in tumors derived from Cav-1 knockout and wild-type 4T1 cells. Correlation analysis and immunoblotting further revealed that Cav-1 might regulate metastasis via integrin α3 (ITGα3). In silico protein docking predicted an interaction between Cav-1 and ITGα3, which was confirmed by co-immunoprecipitation. Furthermore, Cav-1 and ITGα3 knockdown corroborated its role in metastasis in the cell migration assay.
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    Effects of TRPC1’s Lysines on Heteromeric TRPC5-TRPC1 Channel Function
    (MDPI, 2024-12-06) Demaree, Isaac S.; Kumar, Sanjay; Tennessen, Kayla; Hoang, Quyen Q.; White, Fletcher A.; Obukhov, Alexander G.; Anatomy, Cell Biology and Physiology, School of Medicine
    Background: TRPC5 proteins form plasma membrane cation channels and are expressed in the nervous and cardiovascular systems. TRPC5 activation leads to cell depolarization and increases neuronal excitability, whereas a homologous TRPC1 inhibits TRPC5 function via heteromerization. The mechanism underlying the inhibitory effect of TRPC1 in TRPC5/TRPC1 heteromers remains unknown. Methods: We used electrophysiological techniques to examine the roles of subunit stoichiometry and positively charged luminal residues of TRPC1 on TRPC5/TRPC1 function. We also performed molecular dynamics simulations. Results: We found that increasing the relative amount of TRPC1 in TRPC5/TRPC1 heteromers reduced histamine-induced cation influx through the heteromeric channels. Consistently, histamine-induced cation influx was small in cells co-expressing TRPC5-TRPC1 concatemers and TRPC1, and large in cells co-expressing TRPC5-TRPC1 concatemers and TRPC5. Molecular dynamics simulations revealed that the TRPC1 protein has two positively charged lysine residues that are facing the heteromeric channel pore lumen. Substitution of these lysines with asparagines decreased TRPC1's inhibitory effect on TRPC5/TRPC1 function, indicating that these lysines may regulate cation influx through TRPC5/TRPC1 heteromers. Additionally, we established that extracellular Mg2+ inhibits cation influx through TRPC5/TRPC1, contributing to channel regulation. Conclusions: We revealed that the inhibitory effect of TRPC1 on heteromeric TRPC5/TRPC1 function likely involves luminal lysines of TRPC1.
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    Time series modelling and forecasting of Monkeypox outbreak trends Africa's in most affected countries
    (Elsevier, 2024-11-14) Jena, Diptismita; Sridhar, Sathvik Belagodu; Shareef, Javedh; Talath, Sirajunisa; Ballal, Suhas; Kumar, Sanjay; Bhat, Mahakshit; Sharma, Shilpa; Kumar, M. Ravi; Chauhan, Ashish Singh; Gaidhane, Abhay M.; Agarwal, Neha; Bushi, Ganesh; Shabil, Muhammed; Zahiruddin, Quazi Syed; Mohanty, Aroop; Al-Tawfiq, Jaffar A.; Sah, Ranjit; Medicine, School of Medicine
    Background: The recent outbreak of Monkeypox (Mpox), particularly the clade 1b variant, have shifted the epidemiological landscape, making it a Public Health Emergency of International Concern. Africa remains a hotspot with significant ongoing outbreaks, necessitating a focused study on outbreak trends and forecasting to guide health interventions. Methods: This study utilizes a comprehensive dataset from the four most affected African countries, covering weekly and cumulative Mpox cases from August 6, 2023, to August 18, 2024. Time series analysis techniques, including ARIMA models and Join Point Regression, were employed to forecast Mpox trends and analyse the annual percentage change in new cases. Results: Descriptive statistics highlighted significant variability in Mpox cases across the studied regions with the mean cases in Africa at 72.55 and a high standard deviation of 60.885. Forecasting models suggest a continued increase in Mpox cases, with cumulative cases expected to reach 6922.95 by the 65th week (95 % CI: 6158.62 to 7687.27) and new cases projected at 45.93 (95 % CI: -88.17 to 180.04). Conclusion: The study underscores the persistent nature of Mpox outbreaks in Africa and the critical need for continuous surveillance and adaptive public health strategies. The forecasts generated offer valuable insights into potential future trends, aiding in the allocation of resources and the implementation of targeted health interventions to curb the spread of the disease.