Extracellular vesicles as mediators of cell-cell communication in ovarian cancer and beyond - A lipids focus.

Extracellular vesicles (EVs) are messengers that carry information in the form of proteins, lipids, and nucleic acids and are not only essential for intercellular communication but also play a critical role in the progression of various pathologies, including ovarian cancer. There has been recent substantial research characterising EV cargo, specifically, the lipid profile of EVs. Lipids are involved in formation and cargo sorting of EVs, their release and cellular uptake. Numerous lipidomic studies demonstrated the enrichment of specific classes of lipids in EVs derived from cancer cells suggesting that the EV associated lipids can potentially be employed as minimally invasive biomarkers for early diagnosis of various malignancies, including ovarian cancer. In this review, we aim to provide a general overview of the heterogeneity of EV, biogenesis, their lipid content, and function in cancer progression focussing on ovarian cancer.

SAR443809: a selective inhibitor of the complement alternative pathway, targeting complement factor Bb.

Dysregulated activation of the complement system is implicated in the onset or progression of several diseases. Most clinical-stage complement inhibitors target the inactive complement proteins present at high concentrations in plasma, which increases target-mediated drug disposition and necessitates high drug levels to sustain therapeutic inhibition. Furthermore, many efforts are aimed at inhibiting only terminal pathway activity, which leaves opsonin-mediated effector functions intact. We describe the discovery of SAR443809, a specific inhibitor of the alternative pathway C3/C5 convertase (C3bBb). SAR443809 selectively binds to the activated form of factor B (factor Bb) and inhibits alternative pathway activity by blocking the cleavage of C3, leaving the initiation of classical and lectin complement pathways unaffected. Ex vivo experiments with patient-derived paroxysmal nocturnal hemoglobinuria erythrocytes show that, although terminal pathway inhibition via C5 blockade can effectively inhibit hemolysis, proximal complement inhibition with SAR443809 inhibits both hemolysis and C3b deposition, abrogating the propensity for extravascular hemolysis. Finally, intravenous and subcutaneous administration of the antibody in nonhuman primates demonstrated sustained inhibition of complement activity for several weeks after injection. Overall, SAR443809 shows strong potential for treatment of alternative pathway-mediated disorders.

Retinal nerve fiber layer thickness and its correlation with visual symptoms and radiological features in pituitary macroadenoma.

Objective: The aim of the study was to evaluate the association of the thickness of retinal nerve fiber layer (RNFL) with (i) visual symptoms and (ii) suprasellar extension defined by magnetic resonance imaging (MRI) in patients with pituitary macroadenoma. Materials and Methods: RNFL thickness of 50 consecutive patients operated for pituitary macroadenoma between July 2019 and April 2021 were compared with standard visual examination findings and MRI measurements such as optic chiasm height, distance between the optic chiasm and adenoma, suprasellar extension, and chiasmal lift. Results: The study group included 100 eyes of 50 patients operated for pituitary adenomas with suprasellar extension. RNFL thinning predominantly involved the nasal (84.26 ± 16.43 µm) and temporal quadrants (70.72 ± 14.80 µm) and correlated well with the visual field deficit (P < 0.001). Patients with moderate-to-severe deficit in visual acuity had a mean RNFL thickness <85 µm and patients with severe disc pallor had extremely thin RNFLs (<70 µm). Suprasellar extension defined as Wilsons Grade C, D, and E and Fujimotos Grades 3 and 4 were significantly associated with thin RNFLs <85 µm (P < 0.01). Chiasmal lift more than 1 cm and tumor chiasm distance of <0.5 mm were associated with thin RNFL (P < 0.002). Conclusion: RNFL thinning correlates directly with the severity of visual deficits in patients with pituitary adenoma. Wilsons Grade D and E, Fujimoto Grade 3 and 4, chiasmal lift more than 1 cm, and chiasm tumor distance <0.5 mm are strong predictors of RNFL thinning and poor vision. Pituitary macro adenoma and other suprasellar tumors need to be excluded in patients with preserved vision but having obvious RNFL thinning.

Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities.

Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor. Site-specific GI cancers share a few common risk factors; however, they are largely distinct in their etiologies and descriptive epidemiologic profiles. A large number of mutations or copy number changes associated with carcinogenesis are commonly found in noncoding DNA regions, which transcribe several noncoding RNAs (ncRNAs) that are implicated to regulate cancer initiation, metastasis, and drug resistance. In this review, we summarize the regulatory functions of ncRNAs in GI cancer development, progression, chemoresistance, and health disparities. We also highlight the potential roles of ncRNAs as therapeutic targets and biomarkers, mainly focusing on their ethnicity-/race-specific prognostic value, and discuss the prospects of genome-wide association studies (GWAS) to investigate the contribution of ncRNAs in GI tumorigenesis.

Study of antibacterial and antifungal efficacy of platelet-rich fibrin and platelet-rich fibrin matrix.

BACKGROUND: Platelet concentrates are extensively utilized in the medical and dental field to promote tissue regeneration. The profusion of endogenous growth factors in platelets α-granules transmit their use for enhanced wound healing. However, little attention has been given to study their antimicrobial potential. This study was conducted to assess the antibacterial and antifungal property of platelet-rich fibrin (PRF) and PRF matrix (PRFM). MATERIALS AND METHODOLOGY: Blood samples were obtained from 16 participants, PRF and PRFM were processed as per the protocol prescribed by Choukroun et al. and Lucarelli et al., respectively. The susceptibility test against microbiota in the root canal and Candida albicans was assessed through minimum inhibition zone by agar diffusion technique. RESULTS: PRF showed an effective antibacterial property, however, did not perform well against C. albicans strains. PRFM did not show any antibacterial or antifungal properties. CONCLUSIONS: The antibacterial efficacy of PRF may prove beneficial when used in the revascularization procedure of immature necrotic teeth.

Effect of Ethanol Exposure on Slow Wave Activity and Smooth Muscle Contraction in the Rat Small Intestine.

BACKGROUND: Ethanol ingestion causes a variety of gastrointestinal disturbances including motility alterations. Slow wave propagation coordinates gastrointestinal motility, and abnormal slow wave activity is thought to contribute to motility disorders. To date, however, little is known about the effect of acute ethanol on motility disturbances associated with slow wave activity. AIM: To investigate the effect of ethanol on small intestine slow wave activity. METHODS: Segments (3-5 cm long) were isolated from the rat duodenum, jejunum, and ileum and mounted in an organ bath superfused with a normal Tyrode solution or with 1, 3, or 5% ethanol containing Tyrode. The electrical activities were recorded using an array of 121 extracellular electrodes, and motility recordings were performed using a digital video camera. RESULTS: The frequency and amplitude of slow wave activity were not altered at 1, 3, or 5% ethanol concentrations, but a significant drop in velocity was found at 3 and 5% ethanol. Furthermore, inexcitable areas appeared in a dose-dependent manner. Slow wave was sometimes also seen to propagate in a circular fashion, thereby describing a reentrant loop. Finally, in all duodenal, jejunal, and ileal segments, ethanol inhibited contractions and became fully quiescent at 3-5%. CONCLUSIONS: These studies for the first time demonstrate that ethanol significantly inhibits slow wave and spike activity in a dose-dependent manner and could also initiate reentrant activities. Intestinal contractions were also inhibited in a dose-dependent manner. In conclusion, ethanol inhibits both slow wave activity and motor activity to cause ethanol-induced intestinal disturbances.

Enzymatic cleavage of uracil-containing single-stranded DNA linkers for the efficient release of affinity-selected circulating tumor cells.

We report a novel strategy to enzymatically release affinity-selected cells, such as circulating tumor cells (CTCs), from surfaces with high efficiency (∼90%) while maintaining cell viability (>85%). The strategy utilizes single-stranded DNAs that link a capture antibody to the surfaces of a CTC selection device. The DNA linkers contain a uracil residue that can be cleaved.

siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells.

siRNA delivery potential of the Dengue virus capsid protein in cultured cells was recently reported, but target knockdown potential in the context of specific diseases has not been explored. In this study we have evaluated the utility of the protein as an siRNA carrier for anti Dengue viral and anti cancer applications using cell culture systems. We show that target specific siRNAs delivered using the capsid protein inhibit infection by the four serotypes of Dengue virus and proliferation of two cancer cell lines. Our data confirm the potential of the capsid for anti Dengue viral and anti cancer RNAi applications. In addition, we have optimized a fermentation strategy to improve the yield of Escherichia coli expressed D2C protein since the reported yields of E. coli expressed flaviviral capsid proteins are low.

Role of autoimmune responses in periodontal disease.

Periodontal diseases are characterized by localized infections and inflammatory conditions that directly affect teeth supporting structures which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidences of involvement of immunopathology have been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. This review is an attempt to throw light on the etiopathogenesis of periodontal disease highlighting the autoimmunity aspect of the etiopathogenesis involved in the initiation and progression of the disease. However, further clinical trials are required to strengthen the role of autoimmunity as a cause of periodontal disease.

Extramedullary plasmacytoma of gingiva and soft tissue in neck.

Plasmacytoma is a malignant disease that present either in bone marrow (medullary plasmacytoma), within the bone (solitary plasmacytoma of bone), or outside of bone, as the extramedullary plasmacytoma. Extramedullary plasmacytoma accounts for 3% of all plasma cell tumours and approximately 90% of extramedullary plasmacytomas affect the head and neck region commonly affecting the nasal cavity, paranasal sinuses, tonsillar fossa and oral cavity. Multiple extramedullary plasmacytoma is defined when there is more than one extramedullary tumour of clonal plasma cells and such presentations are extremely rare. We report such a rare case of multiple extramedullary plasmacytoma involving gingiva and neck. Here is a case report of a 65-year-old female patient presenting with extramedullary plasmacytoma of the gingiva and soft tissue in neck.

Infant mouse brain passaged Dengue serotype 2 virus induces non-neurological disease with inflammatory spleen collapse in AG129 mice after splenic adaptation.

AG129 mice are known to be permissive to infection by multiple serotypes of Dengue virus (DENV). There exists a concern that mouse passaged strains of the virus may induce neurological complications rather than increased vascular permeability in these mice, hence the use of human clinical isolates of the virus to develop the AG129 mouse model of Dengue disease with increased vascular permeability. The present study evaluated four mouse brain passaged DENV strains, each belonging to a different serotype and three of them having an original isolation history in India, for their suitability to serve as candidates to induce rapid lethal disease in AG129 mice. While all the viruses were able to establish a productive infection in the spleen, none of them induced paralysis despite their mouse brain passage history. Only the type-2 virus acquired the ability to induce a lethal disease after a single round of spleen to spleen passage, and became highly virulent after five more rounds. This apparently non-neurological lethal disease was characterized by high viral burden, elevated vascular permeability, serum TNF-α surge immediately before moribund stage, transient leukocytosis followed by severe leukopenia, lymphopenia throughout the course of the infection, and transient thrombocytopenia. The disease was also characterized by inflammatory splenic collapse during moribund stage, reminiscent of spontaneous splenic rupture reported in rare cases of severe Dengue in humans.

Clinical audit in dentistry: From a concept to an initiation.

Clinical audit is a quality improvement process that aims to improve patient care through a systematic review of care against explicit criteria. It is a cyclic and multidisciplinary process which involves a series of steps from planning the audit through measuring the performance to implementing and sustaining the change. Although audit contains some facets of research, it is essential to understand the difference between the two. Auditing can be done right from the record maintaining, diagnosis and treatment and postoperative evaluation and follow-up. The immense potential of clinical audit can be utilized only when open-mindedness and innovativeness are encouraged and evidence-based work culture is cultivated.