Nanotoxicity of multifunctional stoichiometric cobalt oxide nanoparticles (SCoONPs) with repercussions toward apoptosis, necrosis, and cancer necrosis factor (TNF-α) at nano-biointerfaces.

Introduction: Apoptosis, necrosis, and cancer necrosis factor (TNF-a) are all impacted by the nanotoxicity of multifunctional stoichiometric cobalt oxide nanoparticles (SCoONPs) at nano-biointerfaces. The creation of multi-functional nanoparticles has had a considerable impact on the transport of drugs and genes, nanotheranostics (in-vivo imaging, concurrent diagnostics), interventions for external healing, the creation of nano-bio interfaces, and the instigation of desired changes in nanotherapeutics. Objectives: The quantitative structure-activity relationships, chemical transformations, biological interactions as well as toxicological analyses are considered as main objectives. Discrete dimensions of SCoNPs-cell interaction interfaces, their characteristic physical features (size, shape, shell structure, and surface chemistry), impact on cell proliferation and differentiation are the key factors responsible for nanotoxicity. Methods: The development of multi-functional nanoparticles has been significant in drug/gene delivery, nanotheranostics (in-vivo imaging, coinciding diagnostics), and external healing interventions, designing a nano-bio interface, as well as inciting desired alterations in nanotherapeutics. Every so often, the cellular uptake of multi-functional cobalt [Co, CoO, Co2(CO)8 and Co3O4] nanoparticles (SCoONPs) influences cellular mechanics and initiates numerous repercussions (oxidative stress, DNA damage, cytogenotoxicity, and chromosomal damage) in pathways, including the generation of dysregulating factors involved in biochemical transformations. Results: The concerns and influences of multifunctional SCoNPs on different cell mechanisms (mitochondria impermeability, hydrolysis of ATP, the concentration of Ca2+, impaired calcium clearance, defective autophagy, apoptosis, and necrosis), and interlinked properties (adhesion, motility, and internalization dynamics, role in toxicity, surface hydrophilic and hydrophobicity, biokinetics and biomimetic behaviors of biochemical reactions) have also been summarized. SCoONPs have received a lot of interest among the nanocarriers family because of its advantageous qualities such as biodegradability, biocompatibility, nontoxicity, and nonimmunogenicity. Conclusion: Various applications, such as bio-imaging, cell labeling, gene delivery, enhanced chemical stability, and increased biocompatibility, concerning apoptosis, necrosis, and nano-bio interfaces, along with suitable examples. In this analysis, the multi-functional cobalt [Co, CoO, Co2(CO)8 and Co3O4] nanoparticles (SCoNPs) intricacies (cytogenotoxicity, clastogenicity, and immunomodulatory), nanotoxicity, and associated repercussions have been highlighted and explained.

The Mizoroki-Heck reaction between in situ generated alkenes and aryl halides: cross-coupling route to substituted olefins.

This review covers palladium-catalyzed typical Mizoroki-Heck cross-coupling reactions of aryl halides with in situ generated alkenes, by following a typical Heck coupling mechanism to form substituted olefins unlike direct cross-coupling of alkenes with aryl halides in Heck olefination. These reactions solve the issue of alkenes undergoing polymerization at high temperatures and increase reaction efficiency by reducing the reaction time and purification steps.

Role of Guided FNA in Gallbladder Cancer: A Retrospective 3-Year Study.

Background: A majority of the patients with gall bladder cancer (GBCa) present at an advanced stage and have poor survival. The aim is to retrospectively study the role of guided FNA in the diagnosis of GBCa in a superspecialty institute and to describe the cytomorphologic spectrum of gall bladder (GB) lesions in the North Indian population. Materials and Methods: All suspected cases of GBCa who underwent guided FNA from the primary GB mass or metastatic liver space-occupying lesion from 2017 to 2019 were included. The aspirate smears were retrieved and analyzed for cytomorphological features independently by two cytopathologists. The neoplastic lesions were classified according to the WHO 2019 classification. Results: Of 489 cases, fine needle aspiration cytology (FNAC) was diagnostic in 463 cases (94.6%), of which 417 (90.1%) were positive for malignancy, 35 (7.5%) were inflammatory, and 11 (2.4%) were inconclusive for malignancy. Adenocarcinoma not otherwise specified (NOS) was the most common type seen in 330 cases (79.1%) and 87 (20.9%) were unusual variants. These included papillary adenocarcinoma (22, 5.2%), mucinous adenocarcinoma (12, 2.8%), signet ring carcinoma (2,0.4%), adenosquamous carcinoma (8, 1.9%), squamous cell carcinoma (10, 2.4%), neuroendocrine neoplasms (7, 1.7%), undifferentiated carcinoma (24, 5.7%) and non-Hodgkin lymphoma (2,0.4%), respectively. Immunohistochemistry on the cell block confirmed the diagnosis wherever possible. Histopathology was discordant in 5 out of 33 cases. Conclusion: Guided FNAC is a sensitive investigation that plays a crucial role in confirming the diagnosis and deciding the further treatment options in advanced-stage GBCa patients. The uncommon variants of GBCa can be reliably categorized on cytology.

Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in Northern India.

BACKGROUND: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Indian women. We investigated the distribution and the nature of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of 204 Indian breast cancer patients and 140 age-matched controls. METHOD: Cases were selected with regard to early onset disease (< or =40 years) and family history of breast and ovarian cancer. Two hundred four breast cancer cases along with 140 age-matched controls were analyzed for mutations. All coding regions and exon-intron boundaries of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis followed by direct sequencing of detected variants. RESULTS: In total, 18 genetic alterations were identified. Three deleterious frame-shift mutations (185delAG in exon 2; 4184del4 and 3596del4 in exon 11) were identified in BRCA1, along with one missense mutation (K1667R), one 5'UTR alteration (22C>G), three intronic variants (IVS10-12delG, IVS13+2T>C, IVS7+38T>C) and one silent substitution (5154C>T). Similarly three pathogenic protein-truncating mutations (6376insAA in exon 11, 8576insC in exon19, and 9999delA in exon 27) along with one missense mutation (A2951T), four intronic alterations (IVS2+90T>A, IVS7+75A>T, IVS8+56C>T, IVS25+58insG) and one silent substitution (1593A>G) were identified in BRCA2. Four previously reported polymorphisms (K1183R, S1613G, and M1652I in BRCA1, and 7470A>G in BRCA2) were detected in both controls and breast cancer patients. Rare BRCA1/2 sequence alterations were observed in 15 out of 105 (14.2%) early-onset cases without family history and 11.7% (4/34) breast cancer cases with family history. Of these, six were pathogenic protein truncating mutations. In addition, several variants of uncertain clinical significance were identified. Among these are two missense variants, one alteration of a consensus splice donor sequence, and a variant that potentially disrupts translational initiation. CONCLUSION: BRCA1 and BRCA2 mutations appear to account for a lower proportion of breast cancer patients at increased risk of harboring such mutations in Northern India (6/204, 2.9%) than has been reported in other populations. However, given the limited extent of reported family history among these patients, the observed mutation frequency is not dissimilar from that reported in other cohorts of early onset breast cancer patients. Several of the identified mutations are unique and novel to Indian patients.