REVIEW OF BIOLOGICAL ACTIVITIES OF HYDRAZONES

Hydrazones possess an azomethine  –NHN=CH   group  and are  considered  as derivatives  of aldehydes and  ketones  in which the  oxygen  atom  has  been  replaced  by  the  NNH2 functional group. These are widely studied molecules owing to their ease of preparation  and  diverse  pharmacological  potential.  This  has  led researchers  to  synthesize  different  heterocyclic  compounds bearing  hydrazones.  Medicinal  chemists  across  the  world  have done  immense  work  on  hydrazones  and  developed  agents  with better  activity  and  low  toxicity  profiles.  Following  different synthetic  protocols  and  through  proper  SAR  studies  differently substituted  hydrazones  have  been  developed  and  found  to  be active  against  different  pharmcological  targets.  They  are  known to  possess  different  biological  activities  viz.  antimicrobial,  antiinflammatory,  anticancer,  antimalarial  etc.  These  observations have  been  guiding  for  the  development  of  new  hydrazones  that possess  varied  biological  activities.  The  review  aims  at highlighting the diverse biological activities of hydrazones.Key words: Azomethine, Hydrazones, Pharmacological Potentia

Antimicrobial potential of epigallocatechin-3-gallate (EGCG): a green tea polyphenol

Abstract: The compounding problem of microbial resistance has become a global threat nowadays and demands urgent attention. Given the limited number of clinically proven drugs available, reversion towards compounds from natural resources have become renewed source of interest. Utilization of novel and potent antimicrobial agents with different targets can act as accessories to antibiotic therapy. Considerable amount of research has been conducted on the various advantages of secondary metabolites produced by different plants. Among these, polyphenols have come into sight over the past few decades as a potential source to promote human health. This article summarizes the various health benefits of EGCG, the major component of green tea polyphenols with more emphasis on the anti-microbial properties of EGCG

LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy

Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here, we investigated the role of a novel vascular endothelial‐associated lncRNA (VEAL2) in regulating endothelial permeability. Precise editing of veal2 loci in zebrafish (veal2 (gib005Δ8/+)) induced cranial hemorrhage. In vitro and in vivo studies revealed that veal2 competes with diacylglycerol for interaction with protein kinase C beta‐b (Prkcbb) and regulates its kinase activity. Using PRKCB2 as bait, we identified functional ortholog of veal2 in humans from HUVECs and named it as VEAL2. Overexpression and knockdown of VEAL2 affected tubulogenesis and permeability in HUVECs. VEAL2 was differentially expressed in choroid tissue in eye and blood from patients with diabetic retinopathy, a disease where PRKCB2 is known to be hyperactivated. Further, VEAL2 could rescue the effects of PRKCB2‐mediated turnover of endothelial junctional proteins thus reducing hyperpermeability in hyperglycemic HUVEC model of diabetic retinopathy. Based on evidence from zebrafish and hyperglycemic HUVEC models and diabetic retinopathy patients, we report a hitherto unknown VEAL2 lncRNA‐mediated regulation of PRKCB2, for modulating junctional dynamics and maintenance of endothelial permeability

Mitofusin-2 Negatively Regulates Melanogenesis by Modulating Mitochondrial ROS Generation

Inter-organellar communication is emerging as one of the most crucial regulators of cellular physiology. One of the key regulators of inter-organellar communication is Mitofusin-2 (MFN2). MFN2 is also involved in mediating mitochondrial fusion–fission dynamics. Further, it facilitates mitochondrial crosstalk with the endoplasmic reticulum, lysosomes and melanosomes, which are lysosome-related organelles specialized in melanin synthesis within melanocytes. However, the role of MFN2 in regulating melanocyte-specific cellular function, i.e., melanogenesis, remains poorly understood. Here, using a B16 mouse melanoma cell line and primary human melanocytes, we report that MFN2 negatively regulates melanogenesis. Both the transient and stable knockdown of MFN2 leads to enhanced melanogenesis, which is associated with an increase in the number of mature (stage III and IV) melanosomes and the augmented expression of key melanogenic enzymes. Further, the ectopic expression of MFN2 in MFN2-silenced cells leads to the complete rescue of the phenotype at the cellular and molecular levels. Mechanistically, MFN2-silencing elevates mitochondrial reactive-oxygen-species (ROS) levels which in turn increases melanogenesis. ROS quenching with the antioxidant N-acetyl cysteine (NAC) reverses the MFN2-knockdown-mediated increase in melanogenesis. Moreover, MFN2 expression is significantly lower in the darkly pigmented primary human melanocytes in comparison to lightly pigmented melanocytes, highlighting a potential contribution of lower MFN2 levels to higher physiological pigmentation. Taken together, our work establishes MFN2 as a novel negative regulator of melanogenesis

Multidrug Resistance: An Emerging Crisis

The resistance among various microbial species (infectious agents) to different antimicrobial drugs has emerged as a cause of public health threat all over the world at a terrifying rate. Due to the pacing advent of new resistance mechanisms and decrease in efficiency of treating common infectious diseases, it results in failure of microbial response to standard treatment, leading to prolonged illness, higher expenditures for health care, and an immense risk of death. Almost all the capable infecting agents (e.g., bacteria, fungi, virus, and parasite) have employed high levels of multidrug resistance (MDR) with enhanced morbidity and mortality; thus, they are referred to as “super bugs.” Although the development of MDR is a natural phenomenon, the inappropriate use of antimicrobial drugs, inadequate sanitary conditions, inappropriate food-handling, and poor infection prevention and control practices contribute to emergence of and encourage the further spread of MDR. Considering the significance of MDR, this paper, emphasizes the problems associated with MDR and the need to understand its significance and mechanisms to combat microbial infections

Orai3 Regulates Pancreatic Cancer Metastasis by Encoding a Functional Store Operated Calcium Entry Channel

Store operated Ca2+ entry (SOCE) mediated by Orai1/2/3 channels is a highly regulated and ubiquitous Ca2+ influx pathway. Although the role of Orai1 channels is well studied, the significance of Orai2/3 channels is still emerging in nature. In this study, we performed extensive bioinformatic analysis of publicly available datasets and observed that Orai3 expression is inversely associated with the mean survival time of PC patients. Orai3 expression analysis in a battery of PC cell lines corroborated its differential expression profile. We then carried out thorough Ca2+ imaging experiments in six PC cell lines and found that Orai3 forms a functional SOCE channel in PC cells. Our in vitro functional assays show that Orai3 regulates PC cell cycle progression, apoptosis and migration. Most importantly, our in vivo xenograft studies demonstrate a critical role of Orai3 in PC tumor growth and secondary metastasis. Mechanistically, Orai3 controls G1 phase progression, matrix metalloproteinase expression and epithelial-mesenchymal transition in PC cells. Taken together, this study for the first-time reports that Orai3 drives aggressive phenotypes of PC cells, i.e., migration in vitro and metastasis in vivo. Considering that Orai3 overexpression leads to poor prognosis in PC patients, it appears to be a highly attractive therapeutic target

Papillary Thyroid Carcinoma Presenting with Ulcerated Lymph Node Mass

Papillary thyroid cancer (PTC) is an indolent differentiated thyroid cancer with high risk of cervical lymph node metastasis. It usually presents with thyroid nodule or lateral neck node at level III or IV. Cutaneous involvement by primary thyroid nodule or neck nodes is uncommon. Literature search has shown few cases with fungated thyroid mass and only one case with ulcerated lateral nodal mass. The case report is about management of a rare neglected case of papillary thyroid cancer presenting with large ulcerated lymph node mass involving level IB to V

Data on the mRNA expression by in situ hybridization of Wnt signaling pathway members in the mouse uterus

Wnt signaling plays an important role in uterine organogenesis and oncogenesis. Our mRNA expression data documents the expression of various Wnt pathway members during the key stages of uterine epithelial gland development. Our data illustrates the expression of Wnt signaling inhibitors (Axin2, Sfrp2, Sfrp4, Dkk1 and Dkk3) in mice uteri at postnatal day 6 (PND 6) and day 15 (PND 15). They also describe the expression pattern of the Wnt ligands (Wnt1, Wnt2, Wnt2b, Wnt3, Wnt3a, Wnt5b, Wnt7b, Wnt8a, Wnt8b, Wnt9a, Wnt9b, Wnt10a and Wnt10b) in mice uteri with or without progesterone treatment. Detailed interpretation and discussion of these data is presented in the research article entitled “Differential Wnt signaling activity limits epithelial gland development to the anti-mesometrial side of the mouse uterus” [1]

In-vitro antifungal activity of resorcinol against human fungal pathogen Candida albicans

Abstract: The aim of this study was to evaluate the antifungal potential of Resorcinol (Res) against human fungal pathogen, Candida albicans. In this study, we explored that Res displayed its antifungal potential against two reference strains of C. albicans (ATCC 10261 and ATCC 24433) and five clinical isolates tested. We also showed that Res is equally effective against various non-albicans species of Candida as well thereby demonstrating its wide repertoire. Notably, the antifungal effect of Res seems to be independent of the activity of major drug efflux pumps transporter which is the major cause of drug resistance in C. albicans. Finally, we also demonstrated that Res inhibits the serum and nitrogen starvation dependent yeast to hyphal transition in C. albicans which is one of the major virulence attribute. Taken together, Res exhibited promising in vitro antifungal properties and potent inhibitor of yeast to hyphal transition that could be used for the treatment of Candida infections. Further cellular and in vivo studies are required to explore its precise mechanism of action

Evaluation of HE4 as a prognostic biomarker in uterine cervical cancer,

Introduction: Uterine cervical cancer (UCC) is the fourth most common health problem worldwide among women. Currently available biomarkers CA125, CA199, and CEA for diagnosis or prognostic evaluation of UCC have not got widespread acceptance. Method: Whole blood samples of 64 patients with UCC were collected along with 63 healthy females and tested for serum levels of HE4 (sHE4). A cut-off value for positive result 64.0 pmol/L was set. Statistical analysis of different clinical variables was done. Result: Serum level of HE4 has a significant role in the diagnosis of uterine cervical cancer. Its level increases with age, higher parity (P < 0.05), stage (P < 0.16), tumor size, and parametrial invasion. Negative result was seen with vaginal invasion, lymph node involvement &amp; cases which had recurrence. Various histological types showed variable results. So the serum level of HE4 (sHE) level may play a role in the diagnosis &amp; therapeutic monitoring of UCC. But the prognostic evaluation needs further studies. Conclusion: sHE4 is useful in the diagnosis of cervical cancer, but its prognostic significance is under the question marks. It may be associated with higher values in higher stages. Higher parity of the patient is associated with higher level of HE4 in UCC