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Green light photoactive Ru-based coordination polymer nanoparticles (CPNs), with chemical formula [[Ru(biqbpy)]1.5(bis)](PF6)3 (biqbpy = 6,6′-bis[N-(isoquinolyl)-1-amino]-2,2′-bipyridine; bis = bis(imidazol-1-yl)-hexane), were obtained through polymerization of the trans-[Ru(biqbpy)(dmso)Cl]Cl complex (Complex 1) and bis bridging ligands. The as-synthesized CPNs (50 ± 12 nm diameter) showed high colloidal and chemical stability in physiological solutions. The axial bis(imidazole) ligands coordinated to the ruthenium center were photosubstituted by water upon light irradiation in aqueous medium to generate the aqueous substituted and active ruthenium complexes. The UV-Vis spectral variations observed for the suspension upon irradiation corroborated the photoactivation of the CPNs, while High Performance Liquid Chromatography (HPLC) of irradiated particles in physiological media allowed for the first time precisely quantifying the amount of photoreleased complex from the polymeric material. In vitro studies with A431 and A549 cancer cell lines revealed an 11-fold increased uptake for the nanoparticles compared to the monomeric complex [Ru(biqbpy)(N-methylimidazole)2](PF6)2 (Complex 2). After irradiation (520 nm, 39.3 J/cm2), the CPNs yielded up to a two-fold increase in cytotoxicity compared to the same CPNs kept in the dark, indicating a selective effect by light irradiation. Meanwhile, the absence of 1O2 production from both nanostructured and monomeric prodrugs concluded that light-induced cell death is not caused by a photodynamic effect but rather by photoactivated chemotherapy.

Background: Multidrug Resistance (MDR) among bacteria become a global concern due to failure of antibiotics, is drawn attention for best antimicrobials from the spices which have been using ancient days in Indian culinary and traditional medicine. Aim and Objectives: The present study was undertaken to evaluate the bioactive compounds and their antibacterial activity in routinely used culinary Indian spices against β-lactamase produced MDR bacteria. Material and Methods: Ethanolic extracts prepared from twenty spices and were evaluated for total phenolics, flavonoids, alkaloids, terpenoids, antioxidant properties, and also assayed their antibacterial activities against β-lactamase producing MDR bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus). β-Lactamase and cell viability assays were performed in MDR bacteria. Results: Among twenty spices, cinnamon and clove exhibited highest levels of phenolics and terpenoids with elevated antioxidant potential and also showing greater reducing potential at lower concentrations of extract (2.3 and 4.06 µg GAE/gm), respectively. Further, the spices extracts were assessed for antimicrobial activity against β-lactamase produced tested MDR bacteria and observed higher antimicrobial activity with cinnamon, garlic, tamarind and clove at lowest concentrations of MIC and MBC at 16 - 32 µg GAE/ml, as compared to standard drug, amoxiclav (16/8 µg/ml). Spices significantly inhibited the β-lactamase activity (80–94%) and also cell viability in tested MDR bacteria. Conclusion: Indian spices consist of rich bioactive profile and antioxidant activity inhibited the bacterial growth effectively by suppressing β-lactamase production in MDR bacteria. Results indicating the spices as functional foods and could be used in prevention of antibiotic resistance.

The extracts from sweet sorghum stalk were previously shown to eliminate human colon cancer stem cells (CCSC) in a partial p53-dependent fashion. However, the underlying mechanisms remain unknown. In this study, we transfected CCSC with shRNA against p53 and treated with sweet sorghum phenolics extracted from different plant components. While all sweet sorghum components demonstrated anti-proliferative and pro-apoptotic effects in CCSC, phenolics extracted from the dermal layer and seed head were more potent in eliminating CCSC by elevating caspase 3/7 activity, poly ADP-ribose polymerase cleavage, and DNA fragmentation in a p53-dependent and partial p53-dependent manner, respectively. These effects were associated with decreases in β-catenin, cyclin D1, cMyc, and survivin protein levels. These results suggest that the anti-proliferative and pro-apoptotic effects of sweet sorghum extracts against CCSC are potentially via suppression of Wnt/β-catenin signalling in a p53-dependent (dermal layer) and partial p53-dependent (seed head) manner.

The ruthenium-based photosensitizer (PS) TLD1433 has completed a phase I clinical trial for photodynamic therapy (PDT) treatment of bladder cancer. Here, we investigated a possible repurposing of this drug for treatment of conjunctival melanoma (CM). CM is a rare but often deadly ocular cancer. The efficacy of TLD1433 was tested on several cell lines from CM (CRMM1, CRMM2 and CM2005), uveal melanoma (OMM1, OMM2.5, MEL270), epidermoid carcinoma (A431) and cutaneous melanoma (A375). Using 15 min green light irradiation (21 mW/cm2, 19 J.cm−2, 520 nm), the highest phototherapeutic index (PI) was reached in CM cells, with cell death occurring via apoptosis and necrosis. The therapeutic potential of TLD1433 was hence further validated in zebrafish ectopic and newly-developed orthotopic CM models. Fluorescent CRMM1 and CRMM2 cells were injected into the circulation of zebrafish (ectopic model) or behind the eye (orthotopic model) and 24 h later, the engrafted embryos were treated with the maximally-tolerated dose of TLD1433. The drug was administrated in three ways, either by (i) incubating the fish in drug-containing water (WA), or (ii) injecting the drug intravenously into the fish (IV), or (iii) injecting the drug retro-orbitally (RO) into the fish. Optimally, four consecutive PDT treatments were performed on engrafted embryos using 60 min drug-to-light intervals and 90 min green light irradiation (21 mW/cm2, 114 J.cm−2, 520 nm). This PDT protocol was not toxic to the fish. In the ectopic tumour model, both systemic administration by IV injection and RO injection of TLD1433 significantly inhibited growth of engrafted CRMM1 and CRMM2 cells. However, in the orthotopic model, tumour growth was only attenuated by localized RO injection of TLD1433. These data unequivocally prove that the zebrafish provides a fast vertebrate cancer model that can be used to test the administration regimen, host toxicity and anti-cancer efficacy of PDT drugs against CM. Based on our results, we suggest repurposing of TLD1433 for treatment of incurable CM and further testing in alternative pre-clinical models.

Background: Urinary tract infections (UTIs) are among the most common infectious diseases all over the world. Recent studies reported an increased antibiotic resistance in Escherichia coli, primary causative agent of UTI. The resistance has emerged even to more potent antimicrobial agents like fluoroquinolones. Objectives: The present study was undertaken to evaluate the prevalence and resistance pattern of E.coli causing UTIs in patients admitted to a tertiary care hospital in South India, with reference to fluoroquinolones. Material and Methods: A total of 278 selected urine samples of urinary tract infections were processed for E.coli culture using standard methods. For these urinary E. coli isolates, susceptibility to various antibiotics including fluoroquinolones was checked by Kirby Bauer disk diffusion method according CLSI criteria. Final resistance to fluoroquinolones isolates was analyzed. Results: Out of the 278 selected UTI clinical isolates 148 (54%) showed ciprofloxacin sensitive and 130 (46%) clinical isolates are ciprofloxacin resistant. Of the 130 ciprofloxacin resistant urinary isolates of E. coli subjected to susceptibility test for increased generation of fluoroquinolone drugs, the pattern of resistance noticed as levofloxacin (2nd generation) 79%, gatifloxacin (3rd generation) 77% and moxifloxacin (4th generation) 75%, respectively. The fluoroquinolone resistance in UTI clinical isolates was decreasing with increasing generations of fluoroquinolone. Quinolone drug resistance in clinical isolates was increasing with age and hospitalized patients. Conclusion: Study showed an increased fluoroquinolone resistance among uropathogenic E. coli isolates of UTI. These increased antibiotic resistance trends in UTI patients indicated that it is imperative to rationalize the use of antimicrobials and to use them conservatively.

A novel family of tetraaza macrocyclic Cu(II) complexes [CuLX2] (where L = N4 donor macrocyclic ligands) and (X = Cl−, NO3−) have been synthesized and characterized by elemental analysis, magnetic moments, IR, EPR, mass, electronic spectra and thermal studies. The magnetic moments and electronic spectral studies suggest square planar geometry for [Cu(DBACDT)]Cl2 and [Cu(DBACDT)](NO3)2 complexes and distorted octahedral geometry to the rest of the ten complexes. The biological activity of all these complexes against gram-positive and gram-negative bacteria was compared with the activity of existing commercial antibacterial compounds like Linezolid and Cefaclor. Six complexes out of twelve were found to be most potent against both gram-positive as well as gram-negative bacteria due to the presence of thio group in the coordinated ligands.

Abstract Background Chikungunya (CHIK) fever is a viral disease transmitted to humans by the bite of Chikungunya virus (CHIK virus) infected Aedes mosquitoes. CHIK virus is a member of the Alphavirus genus of the family Togaviridae. Previous reports have indicated that infection with CHIK virus produces an acute arthritis in human hosts by large area of necrosis and collagenosis or fibrosis. Results We carried out the present study to determine the effect of chikungunya on the collagen and connective tissue metabolism in 75 chikungunya-affected people. First, we screened for mucopolysaccharides in urine by Cetyl Trimethyl Ammonium Bromide (CTAB) test. Appearance of heavy precipitate indicates the presence of higher levels of mucopolysaccharides and later quantified by DMB dye method. The urinary mucopolysaccharide in CHIK patients was 342 ± 45 mg/l compared to healthy controls (45 ± 5.6 mg/l). The collagen building blocks, proline and hydroxyproline were also measured in CHIK patients and observed higher excretion compared to healthy controls. Urinary excretions hydroxyproline was greater than the proline levels. Conclusion These results indicate that CHIK virus infection affects and damage the cartilage and connective metabolism and releases the degraded products from the tissue and responsible for increasing the levels of proline, hydroxyproline and mucopolysaccharides in CHIK affected patients.

Long COVID (LC) refers to a condition characterized by a variety of lingering symptoms that persist for more than 4 to 12 weeks following the initial acute SARS-CoV-2 infection. Recent research has suggested that the FOXP4 gene could potentially be a significant factor contributing to LC. Owing to that, this study investigates FOXP4's role in LC by analyzing public datasets to understand its evolution and expression in diverse human populations and searching for drugs to reduce LC symptoms. Population genetic analysis of FOXP4 across human populations unmasks distinct genetic diversity patterns and positive selection signatures, suggesting potential population-specific susceptibilities to conditions like LC. Further, we also observed that FOXP4 experiences high expression during LC. To identify potential inhibitors, drug screening analysis identifies synthetic drugs like Glisoxepide, and natural compounds Kapurimycin A3 produced from Streptomyces sp, and Cucurbitacin B from Begonia nantoensis as promising candidates. Overall, our research contributes to understanding how FOXP4 may serve as a therapeutic target for mitigating the impact of LC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: Since the mid-twentieth century, obesity and its related comorbidities, notably insulin resistance (IR) and type 2 diabetes (T2D), have surged. Nevertheless, their underlying mechanisms remain elusive. Evolutionary medicine (EM) sheds light on these issues by examining how evolutionary processes shape traits and diseases, offering insights for medical practice. This review summarizes the pathogenesis and genetics of obesity-related IR and T2D. Subsequently, delving into their evolutionary connections. Addressing limitations and proposing future research directions aims to enhance our understanding of these conditions, paving the way for improved treatments and prevention strategies., Recent Findings: Several evolutionary hypotheses have been proposed to unmask the origin of obesity-related IR and T2D, e.g., the "thrifty genotype" hypothesis suggests that certain "thrifty genes" that helped hunter-gatherer populations efficiently store energy as fat during feast-famine cycles are now maladaptive in our modern obesogenic environment. The "drifty genotype" theory suggests that if thrifty genes were advantageous, they would have spread widely, but proposes genetic drift instead. The "behavioral switch" and "carnivore connection" hypotheses propose insulin resistance as an adaptation for a brain-dependent, low-carbohydrate lifestyle. The thrifty phenotype theory suggests various metabolic outcomes shaped by genes and environment during development. However, the majority of these hypotheses lack experimental validation. Understanding why ancestral advantages now predispose us to diseases may aid in drug development and prevention of disease. EM helps us to understand the evolutionary relation between obesity-related IR and T2D. But still gaps and contradictions persist. Further interdisciplinary research is required to elucidate complete mechanisms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The synthesis of metal nanoparticles through bio-reduction is environmentally benign and devoid of impurities, which is very important for biological applications. This method aims to improve ZnO nanoparticle's antibacterial and anti-biofilm activity while reducing the amount of hazardous chemicals used in nanoparticle production. The assembly of zinc oxide nanoparticles (ZnO NPs) is presented via bio-reduction of an aqueous zinc nitrate solution using Echinochloacolona (E. colona) plant aqueous leaf extract comprising various phytochemical components such as phenols, flavonoids, proteins, and sugars. The synthesized nano ZnO NPs are characterized by UV-visible spectrophotometer (UV-vis), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (X-RD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and elemental composition by energy-dispersive x-ray spectroscopy (EDX). The formation of biosynthesized ZnO nanoparticles was confirmed by the absorbance at 360-370 nm in the UV-vis spectrum. The average crystal size of the particles was found to be 15.8 nm, as calculated from XRD. SEM and TEM analysis of prepared ZnO NPs confirmed the spherical and hexagonal shaped nanoparticles. ZnO NPs showed antibacterial activity against Escherichia coli and Klebsiella pneumoniae with the largest zone of inhibition (ZOI) of 17 and 18 mm, respectively, from the disc diffusion method. Furthermore, ZnO NPs exhibited significant anti-biofilm activity in a dose-dependent manner against selected bacterial strains, thus suggesting that ZnO NPs can be deployed in the prevention of infectious diseases and also used in food preservation., (© 2024. The Author(s).)

In the present study, we have evaluated the effects of copper (Cu) nanoparticles (NPs) on the primary B-and T-lymphocytes proliferation, cytokine levels, and bio-distribution through in vitro, in vivo and ex-vivo studies to allow the possible exploitations of CuNPs in biomedical applications. CuNPs were characterized by UV-Visible spectroscopy, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). The proliferative response of lymphocytes was studied by 3 H-thymidine incorporation assay and lymphocyte viability through trypan blue assay. The bio-distribution of CuNPs into lymphoid organs was examined by using ex-vivo imaging system. Cytokine levels in plasma of control and CuNPs treated animal groups were determined by enzyme-linked immunosorbent assay (ELISA) method along with other biochemical analysis. CuNPs significantly suppressed the proliferation of primary splenic and thymic lymphocytes in a dose dependent manner. Ex-vivo imaging exhibited the distribution of CuNPs in spleen and thymus. Oral administration of CuNPs (2 mg and 10 mg/kg body weight) significantly inhibited the proliferation of splenic and thymic lymphocytes along with lowered cytokines levels (TNF-alpha and IL-2) on comparison with controls. The results indicated the significant inhibition of lymphocytes proliferative response and secretion of cytokines, thus unveiling the immunomodulatory effects of CuNPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Breast cancer (BC) is the most common cancer and the second leading cause of cancer-related deaths in women globally. Despite advancements in treatment strategies, many patients still develop challenging-to-treat metastatic disease. The development and progression of tumors are influenced by genetic/epigenetic changes within tumor cells and alterations in the tumor microenvironment (TME) through a dynamic communication. The TME comprises various elements, including immune, tumor, and stromal cells. Tumor cells at the core of the TME orchestrate complex signals that lead to tumor growth, survival, and resistance to treatment. Human epidermal growth factor receptor 2 (HER2) is overexpressed in a significant proportion of invasive breast cancers, influencing prognosis and prediction. Novel therapeutic approaches target HER2-positive breast cancers by leveraging HER2-targeted therapeuirtcs such as antibody-drug conjugates, monoclonal antibodies, and tyrosine kinase inhibitors. The TME in HER2-positive breast cancers also involves cancer-associated fibroblasts and cancer-associated adipocytes, which play critical roles in tumor progression and therapy resistance. The immune microenvironment also plays a significant role, with studies indicating its impact on outcomes in HER2-positive breast cancer. Trastuzumab, one of the first monoclonal antibodies targeting HER2, has shown promise in enhancing survival rates in HER2-overexpressing breast cancer. Integration of trastuzumab with chemotherapy has demonstrated significant enhancements in disease-free survival as well as overall survival rates during early breast cancer treatment. Trastuzumab functions by inhibiting HER2 signaling pathways, leading to cell cycle arrest and induction of apoptosis. Overall, understanding the complex interplay between HER2, the tumor microenvironment, and therapeutic interventions is essential for improving outcomes in HER2-positive BC.

In view of Multi-Target Directed Ligand (MTDL) approach in treating Alzheimer's Disease (AD), a series of novel quinazolinone and vanillin cyanoacetamide based acrylamide derivatives ( 9a-z ) were designed, synthesized, and assessed for their activity against a panel of selected AD targets including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), amyloid β protein (Aβ), and also 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and neuroprotective activities. Five of the target analogs 9e , 9h , 9 l , 9t and 9z showed elevated AChE inhibitory activity with IC 50 values of 1.058 ± 0.06, 1.362 ± 0.09, 1.434 ± 0.10, 1.015 ± 0.10, 1.035 ± 0.02 µM respectively, high inhibition selectivity against AChE over BChE and good DPPH radical scavenging activity. Enzyme kinetic studies of the potent hybrids in the series disclosed their mixed inhibition approach. Active analogs were found to be non-toxic on SK-N-SH cell lines and have excellent neuroprotective effects against H 2 O 2 -induced cell death. Strong modulating affinities on Aβ aggregation process were observed for most active compounds since; they irretrievably interrupted the morphology of Aβ 42 fibrils, increased the aggregates and declined the Aβ-induced toxicity in neurons. From the fluorescence emission studies, the binding constants (K) were determined as 2.5 ± 0.021x10 3 , 2.7 ± 0.015x10 3 , 3.7 ± 0.020x10 3 , 2.4 ± 0.013x10 4 , and 5.0 ± 0.033x10 3 M -1 and binding free energies as -5.82 ± 0.033, -6.07 ± 0.042, -6.26 ± 0.015, -7.71 ± 0.024, and -6.29 ± 0.026 kcal M -1 for complexes of AChE- 9e , 9h , 9 l , 9t and 9z , respectively. Moreover, the CD analysis inferred the limited modifications in the AChE secondary structure when it binds to 9e , 9h , 9 l , 9t and 9z . On the basis of docking studies against AChE, the most active congeners were well oriented in the enzyme's active site by interacting with both catalytic active site (CAS) and peripheral anionic site (PAS). In summary, these quinazolinone and vanillin acrylamide hybrid analogs can be used as promising molecular template to further explore their in vivo efficiency in the development of lead compound to treat AD.Communicated by Ramaswamy H. Sarma.

Gynecologic malignancies (GMs) are relatively less focused cancers by oncologists and researchers. The five-year survival rate of patients with GMs remained almost the same during the last decade. The development of drug resistance GMs makes it even more challenging to tackle due to tumor heterogeneity, genomic instability, viral/non-viral antigens, and etiological tumor origin. A precision medicine approach, including gene therapies, is under testing to restore tumor responsiveness to therapeutics and immunotherapy. With more data being uncovered, immunotherapy is emerging as a viable alternative for achieving promising results. This review highlights the drug resistance mechanisms and immunotherapeutic approaches to managing GMs better. The approval of immune therapeutic drugs in recent years shifted this notion. It provided hope for researchers, clinicians, and patients with GMs to experience the anti-cancer benefits of these therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Therapeutic potential and toxic effects of in vivo administered gold nanoparticles (GNPs) and silver nanoparticles (SNP) depend on distribution in tissues. Rhodamine (Rho) labeled bovine serum albumin (BSA) and chitosan (Chi) were prepared by covalent conjugation and were characterized by fluorescence spectral analysis. GNP and SNP were coated with the labeled conjugates of BSA and chitosan by adsorption. The soluble Rho-BSA or Rho-Chi conjugates, uncoated, and conjugate-coated GNP, and SNP were orally administered into 8-week-old rats. After 24 h, rats were euthanized and the liver, kidney, spleen, and thymus were dissected. The tissues were examined ex vivo using a small animal in vivo imaging system. The liver, kidney, and thymus displayed higher fluorescence due to increased accumulation of Rho-BSA or Rho-Chi conjugate-coated nanoparticles (NPs) in the tissues as compared to the spleen where lower fluorescence was noticed. Tissues obtained from rats that were administered Rho-BSA or Rho-Chi conjugate-coated GNP and SNP showed tenfold higher fluorescence intensity as compared to tissues from rats that were given soluble conjugates or NP alone. The results strongly suggest significant tissue distribution of NP following oral administration., (© 2023 Wiley-VCH GmbH.)

To date, numerous nucleotide, amino acid, and codon substitution models have been developed to estimate the evolutionary history of any sequence/organism in a more comprehensive way. Out of these three, the codon substitution model is the most powerful. These models have been utilized extensively to detect selective pressure on a protein, codon usage bias, ancestral reconstruction and phylogenetic reconstruction. However, due to more computational demanding, in comparison to nucleotide and amino acid substitution models, only a few studies have employed the codon substitution model to understand the heterogeneity of the evolutionary process in a genome-scale analysis. Hence, there is always a question of how to develop more robust but less computationally demanding codon substitution models to get more accurate results. In this review article, the authors attempted to understand the basis of the development of different types of codon-substitution models and how this information can be utilized to develop more robust but less computationally demanding codon substitution models. The codon substitution model enables to detect selection regime under which any gene or gene region is evolving, codon usage bias in any organism or tissue-specific region and phylogenetic relationship between different lineages more accurately than nucleotide and amino acid substitution models. Thus, in the near future, these codon models can be utilized in the field of conservation, breeding and medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gupta and Vadde.)

The synthesis of nanometer-sized metallic nanoparticles utilizing bio-sources is one of the most cost-effective and ecologically friendly approaches. Nano-zinc oxide particles (N-ZnO Ps) were made using a simple green synthesis method using an aqueous zinc nitrate salt and Perilla frutescens crude protein as a protecting and reducing agent in the current work. UV-visible (UV-vis) spectrophotometry, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), (energy dispersive x-ray spectroscopy) EDX and high-resolution transmission electron microscopy (HR-TEM) were used to characterize the synthesized N-ZnO Ps. A distinctive UV-vis absorption peak was observed at 370 nm due to N-ZnO Ps. The SEM and HR-TEM pictures revealed N-ZnO Ps with a triangular form. The XRD pattern indicated the wurtzite structure of N-ZnO Ps. Nanoparticles exhibited a zeta potential of -11.3 mV. The antibacterial activity of N-ZnO Ps was tested against Escherichia coli ( E. coli ) and Klebsiella pneumoniae ( K. pneumonia ) microorganisms. The N-ZnO Ps were non-toxic to HMC-3 human normal brain microglia cells; however, they exhibited a potential cytotoxic effect on the LN-18 human brain glioblastoma cell line. These results indicate that N-ZnOPs can act as promising antibacterial and anticancer treatments in the prevention of Glioblastoma.

C(sp 3 )-H alkylation at α-position of methyl-keto group on D-ring of Steroidal diglycoside (SG) with ( i ) C=N of Schiff base imines to form amine derivatives and ( ii ) C=C of acrylate Michael acceptors to form Markovnikov ester products using AuCl 3 /NHC as pre-catalyst and Ag(I) salts as co-catalyst was described. The original form of SG ( 1 ) and its derivatives ( 3b-f & 5a-d) were screened for in vitro anti-cancer activity specifically on two breast cancer cell lines (i.e. MCF-7, MDA-MB-231) and deduced the structure-activity-relationship with the support of molecular docking studies. Among these compounds 3b , 3f , 5b & 5d have shown more potent anticancer activity than standard drug cisplatin with considerable IC50 values.

A one-pot three-component reaction of several 2-ketoaldehydes, secondary amines and terminal alkynes to access 3-aminofurans proceeded well in [bmim][PF 6 ] using a simple and cheap CuI catalyst. The resultant 3-aminofuran products were easily isolated using diethyl ether and the CuI/[bmim][PF 6 ] system was reused six times with a slight decrease in the activity.

Even though the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is related to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), identifying effective and safe therapeutic strategies remains challenging. In search of finding effective treatments to eradicate the virus and improve disease symptoms, scientists are exploring possible therapies such as anti-viral, anti-malaria, immune therapy, and hormone treatments. However, the efficacy of these treatments was not validated on either SARS-CoV or MERS-CoV. In this study, we have reviewed synthetic evidence achieved through systematic and meta-analysis of therapeutics specific for SARS-CoV-2 and observed that the use of the above-mentioned therapies had no clinical benefits in coronavirus disease 2019 patients and, conversely, displayed side effects., Competing Interests: Conflict-of-interest statement: The authors declare no potential conflict of interest for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Recent outbreak of Coronavirus disease (COVID-19) pandemic around the world is associated with 'severe acute respiratory syndrome' (SARS-CoV2) in humans. SARS-CoV2 is an enveloped virus and E proteins present in them are reported to form ion channels, which is mainly associated with pathogenesis. Thus, there is always a quest to inhibit these ion channels, which in turn may help in controlling diseases caused by SARS-CoV2 in humans. Considering this, in the present study, authors employed computational approaches for studying the structure as well as function of the human 'SARS-CoV2 E' protein as well as its interaction with various phytochemicals. Result obtained revealed that α-helix and loops present in this protein experience random movement under optimal condition, which in turn modulate ion channel activity; thereby aiding the pathogenesis caused via SARS-CoV2 in human and other vertebrates. However, after binding with Belachinal, Macaflavanone E, and Vibsanol B, the random motion of the human 'SARS-CoV2 E' protein gets reduced, this, in turn, inhibits the function of the 'SARS-CoV2 E' protein. It is pertinent to note that two amino acids, namely VAL25 and PHE26, play a key role while interacting with these three phytochemicals. As these three phytochemicals, namely, Belachinal, Macaflavanone E & Vibsanol B, have passed the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) property as well as 'Lipinski's Rule of 5s', they may be utilized as drugs in controlling disease caused via SARS-COV2, after further investigation.Communicated by Ramaswamy H. Sarma.

Type 2 diabetes (T2D) is clinically characterized via hyperglycemia. Polymorphism rs5219 in the KCNJ11 gene is a risk factor for developing T2D in humans. KCNJ11 encodes the 'inward-rectifier potassium ion channel (Kir6.2)'. However, because of the absence of the complete crystal/NMR structures of Kir6.2 proteins, insight into its structure and function and its interaction with diverse ligands remain elusive to date. Therefore, a computational approach was employed for predicting the best plausible 'three-dimensional' structure of Kir6.2 as well as for studying the influence of mutation (p. GLU23LYS) on both architectures as well as the function of Kir6.2 employing simulation studies. Results obtained revealed that though, with increased time, 'Gibbs free energy' becomes positive, residues in wild type Kir6.2 experiences less random movement as compared to mutant Kir6.2. The less random movement of residues in wild type Kir6.2 represents the standard coupling between open and closing of 'K ATP channel' and thus the normal secretion of insulin. The more dispersed motion of mutant Kir6.2 residues represents 'overactivity' of the 'K ATP channel' and thus insulin 'under-secretion'. Further, molecular docking and simulation studies identified two phytochemicals/drugs, namely, A-348441 and chushizisin I, which retains the wild type property of Kir6.2 after binding with mutant protein. Unlike A-348441, this is for the first time, the present study is reporting about the plausible anti-diabetic property of chushizisin I. As these two phytochemicals/drugs, namely, A-348441 and chushizisin I, have passed ADMET test, in the near future, they may be utilized as anti-diabetic drugs after further investigation.Communicated by Ramaswamy H. Sarma.

Female-specific cancers are the most common cancers in women worldwide. Early detection methods remain unavailable for most of these cancers, signifying that most of them are diagnosed at later stages. Furthermore, current treatment options for most female-specific cancers are surgery, radiation and chemotherapy. Although important milestones in molecularly targeted approaches have been achieved lately, current therapeutic strategies for female-specific cancers remain limited, ineffective and plagued by the emergence of chemoresistance, which aggravates prognosis. Recently, the application of nanotechnology to the medical field has allowed the development of novel nano-based approaches for the management and treatment of cancers, including female-specific cancers. These approaches promise to improve patient survival rates by reducing side effects, enabling selective delivery of drugs to tumor tissues and enhancing the uptake of therapeutic compounds, thus increasing anti-tumor activity. In this review, we focus on the application of nano-based technologies to the design of novel and innovative diagnostic and therapeutic strategies in the context of female-specific cancers, highlighting their potential uses and limitations., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Hepatocellular carcinoma (HCC) stands third among cancer-related deaths globally. Owing to its high incidence and linked mortality, early diagnosis is alarming for patient survival and the management of patients with developing HCC requires immediate attention. Advances in the knowledge of cancer biology and recognizing unique molecular candidates, including genomic and proteomic profiles, substantiate our understanding about several biological signatures connected with HCC. Precise identification and differential diagnosis of early HCC can remarkably improve patient survival. Currently, detection of HCC in clinical practice is performed by diagnostic imaging and noninvasive methods such as evaluation of serum biomarkers, growth factors, and the like. In this review, we discuss recent developments in targeting biomarkers for HCC.

Neuroblastoma (NBM) is the second leading pediatric cancer that develops from the precursors of the sympathetic nervous system. To date, surgery, chemotherapy, and radiation serve as the first-line treatment against NBM in high-risk patients. However, few of these approaches have severe side effects. Recently, numerous studies have also reported that high chemotherapy doses, along with stem cell rescue, improvise event-free survival in patients. In this review, the authors attempted to discuss the pathogenesis associated with NBM and how stem cell therapy can be employed for the treatment of NBM. Stem cells are a group of multipotent, undifferentiated cells that are capable of producing all cells in a particular tissue, organ, or organism. They have an endogenous self-renewal property. This property is tightly modulated for the normal homeostasis within the body. However, the failure of this process leads to carcinogenesis, including NBM. As these properties are modulated via various intrinsic as well as extrinsic pathways, the arrest of these pathways via various drugs may help in controlling various carcinomas, including NBM. Recently, stem cells were utilized for the diagnosis and treatment of NBM. Nevertheless, most of the studies conducted to date are mainly designed on bulk-cell analysis, which in turn provides little information about the population of cells. Thus, the authors believe that, by employing single-cell RNA sequencing technologies and computational approaches, we can unmask the tumor heterogeneity in NBM in a more comprehensive way. In the near future, this information will be highly useful for the identification of biomarkers and treatment associated with NBM in humans., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The recently developed phylogenomic approach provides a unique way to identify disease risk or protective allele in any organism. While risk alleles evolve mostly under purifying selection, protective alleles are evolving either under balancing or positive selection. Owing to insufficient information, authors employed the phylogenomic approach to detect the nature of selection acting on type 2 diabetes (T2D) genes in Drosophila genus using various models of CODEML utility of PAML. The obtained result revealed that T2D gene sequences are evolving under purifying selection. However, only a few sites in membrane proteins encoded via CG8051, ZnT35C, and kar, are significantly evolving under positive selection under specific scenarios, which might be because of positive or adaptive evolution in response to changing niche, diet or other factors. In the near future, this information will be highly useful in the field of evolutionary medicine and the drug discovery process.

Mutation (p.LEU112PRO) in "carotenoid cleavage dioxygenase 8" (CCD8) protein increases tiller formation in rice plants by cross-talking with auxin and cytokinins. However, owing to the nonexistence of a "three-dimension" structure of CCD8, detail information about its structure and function remain elusive until date. Hence, in the present study, computational approaches were adopted to predict "three-dimensional" (3D) structure of CCD8 protein through comparative modeling techniques and to study the effect of mutation (p.LEU112PRO) on its function as well as architecture through "molecular dynamics" simulation studies. The obtained result reveals that wild-type CCD8 protein is made up of 10 α-helix and 25 β-strands while mutant CCD8 is made up of 11 α-helix and 24 β-strands. Further, molecular docking studies reveals that the wild-type has a better binding affinity with auxin and cytokinin in comparison to mutant. Subsequent molecular dynamics simulation of these four complexes, separately, reveals that the movement of both wild-type as well as mutant CCD8 get reduced after binding with auxin, which in turn prevent auxin transport out of the bud and increases tiller number. However, when cytokinin binds with wild-type and mutant CCD8, it inhibits and enhance CCD8 activity, respectively. As cytokinin positively regulates tiller number formation, enhance activity of mutant CCD8 after binding with cytokinin might be the main reason for more tiller number in mutant than wild-type plant. In the near future, mutant CCD8 along with auxin and cytokinin may be utilized for increasing grain yield in rice plants., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Continuous rise in the human population has resulted in an upsurge in food demand, which in turn demand grain yield enhancement of cereal crops, including rice. Rice yield is estimated via the number of tillers, grain number per panicles, and the number of spikes present per panicle. Marker-assisted selection (MAS) serve as one of the best ways to introduce QTLs/gene associated with yield in the rice plant. MAS has also been employed effectively in dissecting several other complex agricultural traits, for instance, drought, cold tolerance, salinity, etc. in rice plants. Thus, in this review, authors attempted to collect information about various genes/QTLs associated with high yield, including grain number, in rice and how different scheme of MAS can be employed to introduce them in rice ( Oryza sativa L.) plant, which in turn will enhance rice yield. Information obtained to date suggest that, numerous QTLs, e.g., Gn1a , Dep1 , associated with grain number and yield-related traits, have been identified either via mapping or cloning approaches. These QTLs have been successfully introduced into rice plants using various schemes of MAS for grain yield enhancement in rice. However, sometimes, MAS does not perform well in breeding, which might be due to lack of resources, skilled labors, reliable markers, and high costs associated with MAS. Thus, by overcoming these problems, we can enhance the application of MAS in plant breeding, which, in turn, may help us in increasing yield, which subsequently may help in bridging the gap between demand and supply of food for the continuously growing population., Competing Interests: Conflict of interestNone., (© Prof. H.S. Srivastava Foundation for Science and Society 2020.)

Cytokinin oxidase/dehydrogenase (CKX) is the only known enzyme associated with irreversible degradation of cytokinins in plants. CKX2 contains flavin adenine dinucleotide (FAD) domain. Earlier studies utilising antisense & hpRNAi suppression techniques in mutant/transgenic rice plants revealed that when CKX2 binds with FAD, CKX2 expression reduces, which in turn causes cytokinin aggregation in inflorescence meristem that subsequently enhances both branches and grain number resulting in increased grain yield. Owing to the non-existence of complete three-dimensional structure of CKX2, insight into the structure and function of CKX2 and its relationship with its cofactor FAD is still a topic of debate. In the present study, computational approach was employed to estimate the three-dimensional structure of CKX2 through comparative modelling approach. Later, CKX2 and FAD interaction study was performed to understand the underlying mechanism involved with reduced expression of CKX2. Molecular dynamic simulation studies of both CKX2 and CKX-FAD complex revealed that after binding with FAD, CKX2 experienced increased pressure and reduced RMSD, potential energy and free energy landscape energy, which in turn lessen anti-correlation between almost all α and β strands and random motion of C-α, subsequently reducing CKX2 expression. In near future, these information can be utilised for increasing rice yield under irrigated field condition by introgression of Gn1a gene through marker assisted back-crossing breeding. AbbreviationsGROMACSGROningen MAchine for Chemical SimulationsNPTConstant Number of Particles, Volume and TemperatureRMSDRoot Mean Square DeviationRMSFRoot Mean Square FluctuationsQTLquantitative trait lociFADflavin adenine dinucleotideNVTConstant Number of Particles, Pressure and TemperatureLINCSLinear Constraint SolverCKX2Cytokinin oxidase/dehydrogenase 2MM/PBSAMolecular Mechanics/Poisson-Boltzmann surface areaSDFStructure Data FileCommunicated by Ramaswamy H. Sarma.

Background: Coronavirus disease 2019 (COVID-19) is an ongoing, rapidly spreading pandemic caused by Severe Acute Respiratory Syndrome Coronavirus2 (SARS-CoV2). Among all the infected countries around the globe as of now (June 15, 2020), the total confirmed positive cases reported are 7,805,148, with the death of 431,192. At present, no specialized treatments evolved to cure COVID-19. Its treatment is symptomatic. Though huge efforts are being made to produce potential therapies to scuffle COVID-19, no drug has been discovered so far., Objective: Natural products have been playing a significant role in disease control since ancient days. These products serve as templates for designing new anti-microbial agents with a different mechanism of action and also open a door for investigation of effective anti-viral drugs to combat COVID-19. By focusing on this, the authors have narrated the basic structure, infection, and pathogenesis of SARS-CoV2 virus in humans and also reported various natural products or plant-based extracts/bioactive compounds tested against coronaviruses like SARS and MERS, as these viruses are structurally similar to SARS-CoV2 and can be used in designing novel drug against this virus., Conclusion: The natural products having the potential to combat SARS, MERS, and other viruses reviewed in this review article might have anti-viral activities against the SARS-CoV2 virus and can be used directly for further preclinical studies. Therefore, all efforts should be focused on overcoming this serious problem to save many people's lives all over the world., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Polymorphism rs13266634 in SLC30A8 causes abnormal synthesis, maturation and secretion of insulin, resulting in decrease in efficiency of glucose metabolism and diabetes. SLC30A8 encodes Zinc transporter 8 protein (ZnT8). Due to lack of NMR/crystal structures of complete ZnT8 transporter, insights into the structure, function and its interaction with different drugs is still not known. Therefore, in-silico methods were adopted in the present studies for predicting three-dimensional structure of ZnT8 transporter via comparative modelling approach and studying the impact of mutation (p.ARG325TRP) on architecture and function via simulation studies. Wild-type protein comprises 15 α-helix and 3 β-strands, while mutant consists of 12 α-helix and 2 β-strands, respectively. Interaction studies of mutant ZnT8 transporter with phytochemicals/drugs screened the best phytochemicals, which can retain the wild-type property. Molecular docking studies reveal that mutant proteins have better binding energy with ligands of LY-2608204, Roseoside, and Luzonoid B. Further molecular dynamic simulation analysis exhibited a strong binding of these ligands with mutant protein and displaying similar behaviour as that of wild type. ALA79, ILE80, and ARG215 are the common interacting amino acids with ligand in all three complexes. As the ligands passed ADMET tests, these may be utilized as anti-diabetic drugs in near future. Although earlier studies have reported anti-diabetic property of LY-2608204 and Roseoside, for the first time, this study reporting Luzonoid B may have anti-diabetic property besides elucidating the structure and functions of ZnT8 transporter.

Colorectal cancer (CRC) ranks second for incidence in females (third in males). Currently, a broad spectrum of treatment options exists for the treatment of colorectal tumors. However, existing therapeutic options often lead to trauma, side effects, and high cost. Hence, there is an ongoing quest to detect novel approaches for the treatment of colon cancer. Recently, multiple studies have reported that consuming functional foods that are loaded with natural compounds can prevent the risk of CRC. In this review, the authors have attempted to collect information about the best possible foods and their active ingredients that may be used in treatment. Information retrieved through research reveals that all functional foods have aroma, taste, and nutritive value along with active ingredients that are beneficial for human health. For instance, the consumption of red meat increases CRC risk; on the other hand, the consumption of fresh vegetables diminishes such risk. Additionally, plant-based diets comprise fibers, bioactive compounds, and micronutrients, which are reported to have antioxidant as well as anticancer properties. Bioactively rich functional foods have been reported to provide protection against CRC. However, few active components like curcumin work in a dose-dependent manner. Thus, the involvement of medical practitioners during a clinical trial is highly recommended. In general, these active dietary components may aid in improving the health and well-being of patients as well as in managing the risk associated with cancer in a more comprehensive way.

Since human left Africa about 100 thousand years ago, they experienced numerous environmental as well as social transitions. During these transitions, their genome too experiences various forms of selective pressure and retained favorable advantageous alleles in their genome by either positive selection or balancing selection, while removing deleterious alleles through purifying selection. However, when an individual with certain advantageous genetic diversity is migrated to new contrasting environment or lifestyle, the advantageous genetic diversity becomes disadvantageous and finally causing maladaptation. Thus, understanding the role of evolution in adaptation and also in the regulation of population dynamics, is highly important for identifying naturally occurring advantageous or disease risk allele in contemporary populations. Recent advancements in high-throughput sequence technologies have made it easier for understanding the impact of evolutionary forces on the genetic make-up of human in different environmental and social conditions in a far better way. Statistical tests described in this review will enable reader to identify various signatures of balancing selection in different time scales in a more comprehensive way. Additionally, these tests will also help in identifying naturally occurring advantageous or disease risk alleles with applications in animal breeding, nature conservation and human medicine., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Alzheimer's disease (AD) is clinically characterized by the aggregation of neurotoxic amyloid-β (Aβ) peptides in the brain. γ-Secretase catalyzes the reaction of Aβ formation. Inhibition of γ-secretase activating protein (GSAP) reduces Aβ production without disrupting other molecular functions and serves as a promising therapeutic target for lowering Aβ and curing AD. Till date, no proven drug is available for curing AD because of the nonexistence of crystal/NMR structure of GSAP. Thus in the present study, for the first time, we adopted in silico method to predict the 3D structure of GSAP via comparative modeling and studied the architecture and function of GSAP through simulation studies. Docking studies with 4153 phytochemicals revealed that GSAP having a better binding affinity with macaflavanone C, (E)-1-[2,4-dihydroxy-3-(3-methylbut-2-enyl)phenyl]-3-(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)prop-2-en-1-one, and monachosorin B as compared with the standard drug, imatinib. Further, the molecular dynamics analysis suggested that only two phytochemicals, namely, macaflavanone C and (E)-1-[2,4-dihydroxy-3-(3-methylbut-2-enyl)phenyl]-3-(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)prop-2-en-1-one) significantly disrupt the original property of GSAP and also cleared the absorption, distribution, metabolism, and excretion test. These natural compounds may be utilized in future for curing AD after further investigations., (© 2018 Wiley Periodicals, Inc.)

In silico approach was utilised to identify differentially expressed key hub genes during BPH infestation on Bt rice plant, under laboratory conditions. Re-analysis of GSE74745 data with in-house R scripts and STRING database reveals that only 5 key hub genes, namely Os05g0176100, Os06g0683200, Os07g0208500, Os07g0252400 and Os07g0424400, belonging to cellulose synthase family, are differentially expressed and have confidence score ≥0.9 among themselves. Conserve domain analysis of all proteins encoded via these 5 key hub genes reveals that they have a common cellulose synthase domain, in which "Plant-Conserved Region" (PCR) is highly conserved. After binding with other domains of cellulose synthase proteins or other accessory proteins, like sucrose synthase, PCR serves as a metabolic channel to deliver UDP-Glucose, which is the main substrate for cellulose synthesis, into the active site of cellulose synthase and initiate cellulose synthesis. Simulation study of recently solved topological model of PCR [PDB ID: 5JNP] and molecular docking studies of PCR with UDP-glucose reveals that, during BPH infestation, in nearby phloem tissue where BPH suck sap, there is an increase interaction of UDP-glucose with PCR and other accessory proteins which in turn increases both the stability of PCR and the production of cellulose, finally causing callose deposition at that site and hence causing longer nymphal developmental period and lower fertility of BPH infested on Bt rice. In near future, these differentially identified 5 hub genes could be possible targets for controlling BPH infestation in rice plant under field conditions and increasing rice yield globally., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Rice serves as the major food for almost half of the world population. Because of its origin in the tropical and subtropical area, rice is more sensitive towards cold stress. Three homologs of DREB1, namely DREB1A, DREB1B and DREB1C are induced Queryduring cold stress and after binding with GCC-box in the promoter region of the target gene, they enhance cold tolerance in rice plants. Though the majority of DREBs bind GCC-box, the degree of activation varies among DREBs. The protein encoded via these three transcription factors contains a common domain, namely AP2/ERF. In silico method was utilised to predict 3D structure of each AP2/ERF domain. The molecular dynamic analysis suggests, under the normal environmental condition, in each AP2/ERF domain, a positive correlation exists between β-strands and the movement of C-α is constrained. However, during cold stress, when AP2/ERF domain binds with GCC-box present in the promoter region of the target gene, mean pressure of each three AP2/ERF domain gets lowered and final potential energy increases. A positive correlation between β-strands gets disrupted and C-α experiences random movement suggesting enhanced activity of DREB1A, DREB1B and DREB1C during cold stress and enhancement of cold tolerance in plants. Further, MM/PBSA calculations for protein-DNA affinities reveal that, due to lack of α2 in DREB1C, the binding affinity of GCC-box with AP2/ERF domain of DREB1A > DREB1B > DREB1C. Thus, due to a better binding affinity with GCC-box, DREB1A and DREB1B can be utilised in near future for increasing cold tolerance of rice plant and increasing yield.

Brown plant hopper (BPH) is one of the major destructive insect pests of rice, causing severe yield loss. Thirty-two BPH resistance genes have been identified in cultivated and wild species of rice Although, molecular mechanism of rice plant resistance against BPH studied through map-based cloning, due to non-existence of NMR/crystal structures of Bph14 protein, recognition of leucine-rich repeat (LRR) domain and its interaction with different ligands are poorly understood. Thus, in the present study, in silico approach was adopted to predict three-dimensional structure of LRR domain of Bph14 using comparative modelling approach followed by interaction study with jasmonic and salicylic acids. LRR domain along with LRR-jasmonic and salicylic acid complexes were subjected to dynamic simulation using GROMACS, individually, for energy minimisation and refinement of the structure. Final binding energy of jasmonic and salicylic acid with LRR domain was calculated using MM/PBSA. Free-energy landscape analysis revealed that overall stability of LRR domain of Bph14 is not much affected after forming complex with jasmonic and salicylic acid. MM/PBSA analysis revealed that binding affinities of LRR domain towards salicylic acid is higher as compared to jasmonic acid. Interaction study of LRR domain with salicylic acid and jasmonic acid reveals that THR987 of LRR form hydrogen bond with both complexes. Thus, THR987 plays active role in the Bph14 and phytochemical interaction for inducing resistance in rice plant against BPH. In future, Bph14 gene and phytochemicals could be used in BPH management and development of novel resistant varieties for increasing rice yield.

Diabetes mellitus is clinically characterized by hyperglycemia. Though many studies have been done to understand the mechanism of Type 2 Diabetes (T2D), however, the complete network of diabetes and its associated disorders through polygenic involvement is still under debate. The present study designed to re-analyze publicly available T2D related microarray raw datasets present in GEO database and T2D genes information present in GWAS catalog for screening out differentially expressed genes (DEGs) and identify key hub genes associated with T2D. T2D related microarray data downloaded from Gene Expression Omnibus (GEO) database and re-analysis performed with in house R packages scripts for background correction, normalization and identification of DEGs in T2D. Also retrieved T2D related DEGs information from GWAS catalog. Both DEGs lists were grouped after removal of overlapping genes. These screened DEGs were utilized further for identification and characterization of key hub genes in T2D and its associated diseases using STRING, WebGestalt and Panther databases. Computational analysis reveal that out of 99 identified key hub gene candidates from 348 DEGs, only four genes (CCL2, ELMO1, VEGFA and TCF7L2) along with FOS playing key role in causing T2D and its associated disorders, like nephropathy, neuropathy, rheumatoid arthritis and cancer via p53 or Wnt signaling pathways. MIR-29, and MAZ_Q6 are identified potential target microRNA and TF along with probable drugs alprostadil, collagenase and dinoprostone for the key hub gene candidates. The results suggest that identified key DEGs may play promising roles in prevention of diabetes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cancer is a major global health problem with large therapeutic challenges. Although substantial progress has been made in cancer therapy, there still remains a need to develop novel and effective treatment strategies to treat several relapsed and refractory cancers. Recently, there has been growing demand for considering organometallics as antineoplastic agents. This review is focused on a group of organometallics, silver N-heterocyclic carbene complexes (SCCs) and their anticancer efficacy in targeting multiple pathways in various in vitro cancer model systems. However, the precise molecular mechanism of SCCs anticancer properties remains unclear. Here, we discuss the SCCs chemistry, potential molecular targets, possible molecular mechanism of action, and their application in cancer therapies., (© 2018 Wiley Periodicals, Inc.)

Recently, several studies have reported endocrine properties in adipose tissues. The adipose tissue has also been reported to be associated with thermal insulation, mechanical protection, energy storage and release, immune responses, and nonshivering thermogenesis. In the present review, the authors attempted to understand the way in which the adipose tissue is associated with the initiation and modulation of both adaptive and innate immune responses. The information collected from the literature published to date suggests that in an obese individual, the adipose tissue undergoes inflammation. This process leads to insulin resistance, thereby causing various metabolic syndromes, including type 2 diabetes. Apart from the adipocytes, the adipose tissue is also reported to be comprised of a distinct set of immune cells. These immune cells are associated with both innate and adaptive immune responses. Additionally, immune-related structures, for instance, fat-related lymphoid clusters and lymph nodes, are also found in adipose tissues. These additional structures behave as a secondary lymphoid organ and are responsible for modulating the adaptive immune response. Thus, the adipose tissue serves as an active immunological organ and also has the capability of modulating the whole-body metabolism via endocrine and paracrine mechanisms. Nevertheless, it is still unclear if the immune cells present in the adipose tissue have a direct function in the host defense mechanisms. In the near future, unmasking the interactions among the adipocytes and leukocytes may enable us to identify clinically essential pathways that may help in controlling the adipose inflammation, which in turn, might help us manage various metabolic disorders.

Pancreatic cancer is the eleventh most common cancer type and the seventh leading cause of cancer mortality globally. Although chemotherapy is widely employed in the treatment of any cancer type, the response rate in pancreatic cancer is very low. Hence, new and effective techniques in the treatment of pancreatic cancer are needed. Recent advances in molecular profiling as well as high-throughput sequencing technologies, for example, next-generation sequencing technologies, have revolutionized the field of cancer research. Protein-protein interaction among cancer and normal cells plays an important role in any cancer molecular mechanisms, and identifying key genes or protein via experimental technologies requires huge expenditures of capital and time. Thus, integrated computational approaches are urgently needed in cancer research. In this review, we discuss different computational approaches developed to detect novel key genes (TRIM24, CDK14, ECT2 and PSRC1), miRNA (e.g., miR-424, miR-203, miR-1266, miR-1293, and miR-4772), and pancreatic cancer drugs (e.g., trifluoperazine dihydrochloride and trifluoperazine). In the near future, the information presented here will be highly useful in the early diagnosis as well as treatment of pancreatic malignancy.

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human., Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans., Conclusion: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery & radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Colorectal cancer is the third important cause of cancer-associated deaths across the world. Hence, there is an urgent need for understanding the complete mechanism associated with colorectal cancer, which in turn can be utilized toward early detection as well as the treatment of colorectal cancer in humans. Though colorectal cancer is a complex process and chemotherapy is the first step toward the treatment of colorectal cancer, recently several studies suggested that dietary phytochemicals may also aid significantly in reducing colorectal cancer risk in human. However, only few phytochemicals, specifically curcumin derived from the rhizomes of Curcuma longa, have better chemotherapeutic property, which might be because of its ability to regulate the activity of key factors associated with the initiation, promotion, as well as progression of tumors., Objectives: In the present review, the authors made an attempt to summarize the physiochemical properties of curcumin, which in turn prevent colorectal cancer via regulating numerous cell signaling as well as genetic pathways., Conclusion: Accumulated evidence suggested that curcumin suppresses tumour/colon cancer in various ways, (a) restricting cell cycle progression, or stimulating apoptosis, (b) restricting angiogenesis, anti-apoptotic proteins expression, cell survival signaling pathways & their cross-communication and (c) regulating immune responses. The information discussed in the present review will be useful in the drug discovery process as well as the treatment and prevention of colorectal cancer in humans., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)