Gender difference in response to COVID vaccination; a letter to the editor on current findings

Implication for health policy/practice/research/medical education: This study found a difference in the immune response to the COVID vaccine between men and women. Women will have a more robust immune response and show more complications

Downregulation of RhoGDIα increased migration and invasion of ER+ MCF7 and ER− MDA-MB-231 breast cancer cells.

Rho GDp dissociation inhibitors (RhoGDIs) can inhibit cell motility, invasion, and metastasis in cancer by inactivating the RhoGTpases. A member of RhoGDI family has been consistently shown to interact with estrogen receptor (eR), and change its transcriptional activity. eR is a receptor known to be inversely correlated with cell motility and invasion in breast cancer. The consequence of RhoGDIα activity on migration and invasion of eR+ and eR− breast cancers is not clear. The aim of our study was to investigate the possible opposing effect of RhoGDIα on the migration and invasion of eR+ MCF7 and eR− MDA-MB-231 breast cancer cells. RhoGDIα was downregulated using short interfering RNA (siRNA) and upregulated using GFp-tagged ORF clone of RhoGDIα, and their ability for migration and invasion was assayed using transwell chambers. It was found that the silencing of RhoGDIα in MCF7 and MDA-MB-231 cells significantly increased migration and invasion of these cells into the lower surface of porous membrane of the chambers. Overexpression of RhoGDIα in MCF7 cells suppressed their migration and invasion, but no significant effect was found on MDA-MB-231 cells. Our results indicate that the downregulation of RhoGDIα similarly affects the in vitro migration and invasion of eR+ MCF7 and eR− MDA-MB-231 cells. however, our assays are differently affected by the upregulation of RhoGDIα in these two cell lines and this may be due to the differences in eR expression, primary invasive ability and/or other molecules between these two cell line models which warrant further investigation

Differentially expressed proteins in ER+ MCF7 and ER- MDA- MB-231 human breast cancer cells by RhoGDI-α silencing and overexpression

Background: The consequence of Rho GDP dissociation inhibitor alpha (RhoGDIα) activity on migration and invasion of estrogen receptor positive (ER+) and negative (ER-) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDIα and other proteins interacting directly or indirectly with RhoGDIα in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest. Materials and Methods: ER+ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/timeof- flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDIα using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDIα. Results: The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDIα in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDIα in MCF7, while only one protein was identified in the upregulation of RhoGDIα in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-α activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells. Conclusions: Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDIα with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration

T-helper Type 1 and 2 Cytokine Levels in Patients with Benign and Malignant Salivary Gland Tumors

ABSTRACT Background: Salivary gland tumors are among malignancies that have high recurrence rate. Immune responses in salivary gland tumors have not been well elucidated. T helper type 1 (Th1) and Th2 cytokines have been reported to play a role in the outcome of head and neck cancers. Objective: To evaluate the serum levels of interferon gamma (IFN-γ), as the hallmark of Th1 cytokines, and interleukin-4 (IL-4), as the hallmark of Th2 cytokines, in patients with benign and malignant salivary gland tumors in comparison with healthy controls. Methods: Fifty patients with benign and 14 patients with malignant salivary gland tumors, as well as 23 healthy individuals were recruited. Serum levels of IFN-γ and IL-4 were measured using ELISA method. Nonparametric tests were used for data analysis. Results: Serum levels of IFN-γ and IL-4 were found not to be significantly different in patients compared to the control group (0.68 ± 0.29 vs. 1.03 ± 0.57 pg/ml, p=0.58 for IFN-γ, 4.57 ± 1.57 vs. 4.41 ± 1.31 pg/ml, p=0.28 for IL-4). IFN-γ and IL-4 serum levels were also not significantly different between patients with benign and malignant salivary gland tumors (p=0.54 and p=0.86, respectively). Conclusion: The systemic levels of IL-4 and IFN-γ seem not to be associated with salivary gland tumor in our study. Investigation of other cytokines produced by Th1 and Th2 cells are warranted

Umbelliprenin induced both anti-inflammatory and regulatory cytokines in C57/BL6 mice

Objective(s): Umbelliprenin is a prenyloxy-coumarin with pharmacologically polyvalent activity. Several studies have shown its anti-inflammatory, anti-tumor, antioxidant, and antigenotoxic activity, and other functions. However, the exact mechanism of action of this compound on the immune response has not yet been shown. Here, we investigated umbelliprenin effects on the predominance of Th1 and Th2 responses in normal C57/BL6 mice. Materials and Methods: Umbelliprenin (2.5 mg/200 µl IP) were administered to six C57/BL6 mice every other day for 8 days. Paraffin and PBS-injected mice were enrolled as solvent and control groups, respectively (n=6 mice/group). IL-10, IFN-γ, and IL-4 levels were determined in sera and also in splenocytes culture supernatants in the presence of Con A (3 µg/ml) after 72 hr. H&E staining of paraffin embedded blocks was performed for lung and liver tissues of mice. Results: Umbelliprenin could significantly increase the secretion of IFN-γ and IL-4 in sera and IL-10 in splenocytes cultures. Comparison of IFN-γ /IL-4 in the sera and splenocytes culture supernatants showed lower ratios in umbelliprenin treated mice than in solvent and untreated groups. Conclusion: The in vivo study showed that umbelliprenin could induce anti-inflammatory responses via the predominance of Th2 cells and some regulatory responses in C57/BL6 mice

Ten-Year Trends of Utilizing Palliative Care and Palliative Procedures in Patients With Gastric Cancer in the United States From 2009 to 2018 - A Nationwide Database Study

Objectives: Little is known about the current status and the changing trends of hospitalization and palliative care consultation of patients with gastric cancer in the United States. The aim of this study was to evaluate the changing trend in the number of hospitalization, palliative care consultation, and palliative procedures in the US during a recent 10-year period using a nationwide database. Methods: This was a retrospective study that analyzed the National Inpatient Sample (NIS) database of 2009–2018. Patients aged more than 18 years who were diagnosed with a gastric cancer using International Classification of Diseases (ICD)-9 and 10 codes were included. Palliative care consultation included palliative care (ICD-9, V66.7; ICD-10, Z51.5) and advanced care planning (ICD-9, V69.89; ICD-10, Z71.89). Palliative procedures included percutaneous or endoscopic bypass, gastrostomy or enterostomy, dilation, drainage, nutrition, and irrigation for palliative purpose. Results and discussion: A total of 86,430 patients were selected and analyzed in this study. Using a compound annual growth rate (CAGR) approach, the annual number of hospitalizations of gastric cancer patients was found to be decreased during 2009–2018 (CAGR: -0.8%, P = 0.0084), while utilization rates of palliative care and palliative procedures increased (CAGR: 9.3 and 1.6%, respectively; P \u3c 0.0001). Multivariable regression analysis revealed that palliative care consultation was associated with reduced total hospital charges (−$34,188, P \u3c 0.0001). Conclusion: Utilization of palliative care consultation to patients with gastric cancer may reduce use of medical resources and hospital costs

Systemic lupus erythematosus following SARS-CoV-2 vaccination; a review of literature

From March 2020, the coronavirus disease 2019 (COVID-19) pandemic challenged public health and healthcare systems worldwide. Viral infection is one of the environmental factors that has been associated with the development, relapse, or exacerbation of systemic lupus erythematosus (SLE). SLE patients are at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of immune system dysfunction related to their disease as well as immunosuppression medications. So far, the most effective way to reduce SARS-CoV-2 infection-induced hospitalization and death is vaccination. On the other hand, SLE patients present distinct challenges related to the safety and effectiveness of SARS-CoV-2 vaccination. We have reviewed some reports on the onset or flare of SLE post-COVID-19 vaccination. Of note, the mRNA COVID-19 vaccines are associated with increased SLE disease activity, more frequently than the other types of COVID-19 vaccines

Correlation of Circulating Omentin-1 with Bone Mineral Density in Multiple Sclerosis: The Crosstalk between Bone and Adipose Tissue

BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of osteoporosis and fractures. Adipose tissue-derived adipokines may play important roles in the osteoimmunology of MS. In order to determine whether omentin-1 and vaspin may be related to bone health in MS patients, we compared circulating levels of these recently identified adipokines, between MS patients and healthy controls. METHODS: A total of 35 ambulatory MS patients with relapsing-remitting courses were compared with 38 age- and sex-matched healthy controls. Bone mineral density (BMD) was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy x-ray absorptiometry. Circulating omentin-1, vaspin, osteocalcin, osteopontin, osteoprotegerin, the receptor activator of nuclear factor-κB ligand, matrix metalloproteinase 9, C-reactive protein and 25-hydroxy vitamin D levels were evaluated by highly specific enzyme-linked immunosorbent assay methods. RESULTS: There was no significant difference between the two groups regarding bone-related cytokines, adipocytokines, and the BMD measurements of patients with MS and the healthy controls. However, in multiple regression analysis, serum omentin-1 levels were positively correlated with BMD at the femoral neck (β = 0.49, p = 0.016), total hip (β = 0.42, p = 0.035), osteopontin (β = 0.42, p = 0.030) and osteocalcin (β = 0.53, p = 0.004) in MS patients. No correlations were found between vaspin, biochemical, and BMD measures in both groups. CONCLUSIONS: Elevated omentin-1 serum levels are correlated with BMD at the femoral neck and the serum levels of osteocalcin and osteopontin in MS patients. Therefore, there is crosstalk between adipose tissue and bone in MS