Peripartum outcomes and immune responses after SARS-CoV-2 infection in the third trimester of pregnancy.

Background: SARS-CoV-2 infection in pregnant women during the third trimester resulted in overall adverse pregnancy outcomes compared to non-infected controls and a unique humoral and cellular response at delivery. In this study we aimed to assess the impact of SARS-CoV-2 infection on maternal/neonatal peripartum outcomes andimmunological profiles.

Method: In this study, we recruited 304 SARS-CoV-2 infected pregnant women and 910 SARS-CoV-2 non-infected pregnant women who were admitted for delivery.

MDSCs in pregnancy and pregnancy-related complications: an update†.

Maternal-fetal immune tolerance is a process that involves complex interactions of the immune system, and myeloid-derived suppressor cells have emerged as one of the novel immunomodulator in the maintenance of maternal-fetal immune tolerance. Myeloid-derived suppressor cells are myeloid progenitor cells with immunosuppressive activities on both innate and adaptive cells through various mechanisms. Emerging evidence demonstrates the accumulation of myeloid-derived suppressor cells during healthy pregnancy to establish maternal-fetal immune tolerance, placentation, and fetal-growth process.

Enhancing the Bioactivity of Bicyclic Peptides Targeted to Grb7-SH2 by Restoring Cell Permeability.

The development of peptide inhibitors against intracellular targets depends upon the dual challenge of achieving a high affinity and specificity for the target and maintaining cellular permeability for biological activity. Previous efforts to develop bicyclic peptides targeted to the Grb7 signalling protein implicated in HER2+ve cancer progression have resulted in improved affinity. However, these same peptides demonstrated a lowered activity due to their decreased ability to penetrate cell membranes.

The abnormal expression of Tim-3 is involved in the regulation of myeloid-derived suppressor cells and its correlation with preeclampsia.

Introduction: Maternal immune system tolerance to the semi-allogeneic fetus is critical to a successful pregnancy. We previously reported that myeloid-derived suppressor cells (MDSC) was associated with maternal immune imbalance. T cell immunoglobulin and mucin-containing protein 3 (Tim-3)/Galectin-9 (Gal-9) pathway modulates function of various immune cells in maternal-fetal interface.

Structure of the PCBP2/stem-loop IV complex underlying translation initiation mediated by the poliovirus type I IRES.

The poliovirus type I IRES is able to recruit ribosomal machinery only in the presence of host factor PCBP2 that binds to stem-loop IV of the IRES. When PCBP2 is cleaved in its linker region by viral proteinase 3CD, translation initiation ceases allowing the next stage of replication to commence. Here, we investigate the interaction of PCBP2 with the apical region of stem-loop IV (SLIVm) of poliovirus RNA in its full-length and truncated form.

Partners of wild type Grb7 and a mutant lacking its calmodulin-binding domain.

Growth factor receptor bound protein 7 (Grb7) is a mammalian adaptor protein participating in signaling pathways implicated in cell migration, metastatic invasion, cell proliferation and tumor-associated angiogenesis. We expressed tagged versions of wild type Grb7 and the mutant Grb7Δ, lacking its calmodulin-binding domain (CaM-BD), in human embryonic kidney (HEK) 293 cells and rat glioma C6 cells to identify novel binding partners using shot-gun proteomics. Among the new identified proteins, we validated the ubiquitin-ligase Nedd4 (neural precursor cell expressed developmentally down-regulated protein 4), the heat-shock protein Hsc70/HSPA8 (heat shock cognate protein 70) and the cell cycle regulatory protein caprin-1 (cytoplasmic activation/proliferation-associated protein 1) in rat glioma C6 cells.

Metformin exhibits its therapeutic effect in the treatment of pre-eclampsia via modulating the Met/H19/miR-148a-5p/P28 and Met/H19/miR-216-3p/EBI3 signaling pathways.

Metformin (Met) has been found to modify the methylation of H19 and to alter its expression. In addition, IL-27, one of the downstream factors in the H19 signaling pathway, plays an important role in the pathogenesis of pre-eclampsia (PE). In this study, we investigated the molecular mechanism underlying the therapeutic effect of Met in the management of PE both in vivo and in vitro.

Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair.

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs.

Long noncoding RNA lncARSR promotes epithelial ovarian cancer cell proliferation and invasion by association with HuR and miR-200 family.

Epithelial ovarian cancer (EOC) is the fifth leading cause of female cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators in various biological processes through diverse mechanisms. Recently, lncRNA Activated in RCC with Sunitinib Resistance (lncARSR) has been reported to be upregulated and involved in sunitinib resistance of renal cell carcinoma cells.

A first-in-class inhibitor, MLN4924 (pevonedistat), induces cell-cycle arrest, senescence, and apoptosis in human renal cell carcinoma by suppressing UBE2M-dependent neddylation modification.

Purpose: MLN4924 is a second-generation inhibitor that targets ubiquitin-proteasome system by inhibiting neddylation activation enzyme (NAE), and subsequently blocking the neddylation-dependent activation of Cullin-RING E3 ligases (CRLs), which leads to the accumulation of CRLs substrates and hence, suppressing diverse tumor development. In this study, we investigated the potential application of this first-in-class inhibitor MLN4924 in the treatment of human renal cell carcinoma both in vitro and in vivo.

Methods: The impact of MLN4924 on renal cancer cells was determined by measuring viability (MTS), proliferation cell count test and clonogenic assays, cell cycle progression (flow cytometry with propidium iodide staining), apoptosis (flow cytometry with annexin V-FITC labeling) and DNA damage (immunofluorescent staining).

Combined roles of ATP and small hairpin RNA in the activation of RIG-I revealed by solution-based analysis.

RIG-I (retinoic acid inducible gene-I) is a cytosolic innate immune protein that senses viral dsRNA with a 5'-triphosphate overhang. Upon interaction with dsRNA a de-repression of the RIG-I CARD domains takes place that ultimately leads to the production of type I interferons and pro-inflammatory cytokines. Here we investigate the RIG-I conformational rearrangement upon interaction with an activating 5'-triphosphate-10-base pair dsRNA hairpin loop (10bp) compared with a less active 5'-triphosphate-8-base pair dsRNA hairpin loop (8bp).

Eosinophilia-Associated Coronary Artery Vasospasm in Patients with Aspirin-Exacerbated Respiratory Disease.

Background: Some patients with aspirin-exacerbated respiratory disease (AERD) and eosinophilia report angina-type chest pain that occurs at rest and responds to corticosteroid therapy. The frequency of eosinophilia-associated coronary artery vasospasm in patients with AERD, a disease characterized by blood and respiratory tissue eosinophilia, however, is unknown.

Objective: The objective of this study was to understand the cause of the chest pain described above and determine the most appropriate treatment for it.

Genetic analysis of consanguineous families presenting with congenital ocular defects.

Anophthalmia and microphthalmia (A/M) are a group of rare developmental disorders that affect the size of the ocular globe. A/M may present as the sole clinical feature, but are also frequently found in a variety of syndromes. A/M is genetically heterogeneous and can be caused by chromosomal aberrations, copy number variations and single gene mutations.

The emerging role of extracellular vesicles as biomarkers for urogenital cancers.

The knowledge gained from comprehensive profiling projects that aim to define the complex genomic alterations present within cancers will undoubtedly improve our ability to detect and treat those diseases, but the influence of these resources on our understanding of basic cancer biology is still to be demonstrated. Extracellular vesicles have gained considerable attention in past years, both as mediators of intercellular signalling and as potential sources for the discovery of novel cancer biomarkers. In general, research on extracellular vesicles investigates either the basic mechanism of vesicle formation and cargo incorporation, or the isolation of vesicles from available body fluids for biomarker discovery.

CD44v6 expression in primary breast carcinoma in western India: a pilot clinicopathologic study.

Aims And Background: In India, breast cancer is becoming the number one cancer in females. CD44 is believed to play a critical role in the metastatic process, and its spliced forms, especially CD44v6, bestow a metastatic phenotype onto non-metastatic cells. However, the biological significance of CD44v6 in tumor progression remains controversial.

Prognostic significance of molecular markers in oral squamous cell carcinoma: a multivariate analysis.

Background: Multiple marker accumulation impacts tumor progression and biologic phenotypes affect clinical outcome of patients with head and neck cancer. Hence, this study investigated a battery of molecular markers that may help to reflect biologic aggressiveness and predict prognosis.

Methods: Epidermal growth factor receptor (EGFR), Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb, Ki-67, and Bcl-2 were localized immunohistochemically in 135 oral squamous cell carcinoma patients to assess prognostic value.

Improvement in glycemic control and outcome corresponding to intensive insulin therapy protocol development.

Background: Intensive insulin therapy (IIT) has been shown to reduce mortality and morbidity in longer stay, critically ill patients. However, this has been demonstrated in a single site, whereas two multicentric studies have been terminated prematurely mainly due to hypoglycemia. Other difficulties with IIT include efficacy of glycemic control.

Expression of C-Myc mRNA in squamous cell carcinoma of the tongue.

Background: The aim of this study was to evaluate clinical significance of C-myc mRNA in patients with tongue cancer.

Methods: C-myc mRNA expression was studied by RT-PCR in peripheral blood of 25 tongue cancer patients and 24 controls. C-myc protein expression was studied by immunohistochemistry.

High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib.

Background: Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor that induces an early and dramatic response in 10% of patients with advanced nonsmall cell lung carcinoma (NSCLC). Long- term outcome and patterns of disease recurrence after response have not been described.

Methods: The authors evaluated 139 patients with NSCLC treated with gefitinib at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1998 and 2002.

Practical management of patients with non-small-cell lung cancer treated with gefitinib.

Purpose: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs.

Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer.

Purpose: Gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, induces radiographic regressions and symptomatic improvement in patients with non-small-cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response. We undertook this analysis to identify additional clinical and pathologic features associated with sensitivity to gefitinib.

Antitumor activity and tolerability of gefitinib in patients with non-small-cell lung cancer treated in an expanded access program.

We present a series of cases that illustrate potential benefits of the targeted agent gefitinib for patients with advanced and heavily pretreated non-small-cell lung cancer (NSCLC). In 2 phase II clinical trials, 250 mg/day of gefitinib produced objective tumor response rates of 18% and 11%, with excellent tolerance in patients with advanced NSCLC who had previously received standard chemotherapy. Treatment with gefitinib also led to improvements in disease-related symptoms in approximately 40% of cases.

Controversies in differentiating thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

The diagnoses of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) often remain questionable, forcing the clinician to make the difficult decision of initiating therapy based on symptomatology and clinical judgment and, sometimes, instinct. An increased awareness of characteristic symptoms and early diagnoses of TTP and HUS are of utmost importance, given the excellent results obtained with prompt plasma exchange therapy. Tremendous progress has been made in understanding TTP and HUS since TTP was first described more than 75 years ago at Mount Sinai.