Comparative Analysis of Growth and Physiological Responses of Sugarcane Elite Genotypes to Water Stress and Sandy Loam Soils.

Stumpy irrigation water availability is extremely important for sugarcane production in Pakistan today. This issue is rising inversely to river flow due to inadequate water distribution and an uneven rainfall pattern. Sugarcane growth faces a shortage of available water for plant uptake due to the low water-holding capacity of sandy loam soil, particularly under conventional flood irrigation methods. To address this problem, sugarcane clones were evaluated for their agronomic and physiological traits under conditions of low water availability in sandy loam soil. Ten cane genotypes, HSF-240, SPF-213, CPF-249, CP 77-400, S2008-FD-19, S2006-US-469, S2007-AUS-384, S2003-US-633, S2003-US-127, and S2006-US-658, were exposed to four levels of water deficit created through skip irrigations. These deficit levels occurred during the 9th, 11th, 13th, and 16th irrigations at alternate deficit levels between 2020 and 2022. Physiological data were collected during the tillering and grand growth stages (elongation) in response to the water deficit. The sugarcane clones S2006-US-658, S2007-AUS-384, and HSF-240 exhibited resistance to low water availability at both the tillering and grand growth stages. Following them, genotypes S2006-US-658, S2007-AUS-384, and HSF-240 performed better and were also found to be statistically significant. Clones susceptible to water deficit in terms of growth and development were identified as CP 77-400, S2008-FD-19, S2006-US-469, and S2003-US-633. These genotypes showed reduced photosynthetic rate, transpiration rate, stomatal conductance, relative water content, cane yield, and proline content under stressed conditions. Therefore, genotypes S2006-US-658, S2007-AUS-384, and HSF-240 were better performers concerning physiological traits under water deficit and sandy loam soil in both years. Moreover, a significant positive correlation was assessed between agronomic traits and photosynthetic rats. This study highlights that sugarcane can sustain its growth and development even with less irrigation frequency or moisture availability, albeit with certain specific variations.

Maternal and developmental toxicity of Bisphenol-A in SWR/J mice.

Bisphenol-A (BPA), an organic compound with two phenol functional groups, is a widely used industrial plasticizer with known estrogenic properties. It is used in the manufacture of epoxy resins and polycarbonate plastics. This study was designed to evaluate and assess the possible toxicity arising from the oral administration of BPA to pregnant mice. Pregnant SWR/J mice (15 mice/group) were administrated oral doses of BPA (125, 250 and 500 mg/kg/day) over the course of five-day intervals during gestation (D1-5, D6-10 and D11-15), while control groups received only corn oil. The results indicated that BPA was associated with a reduction in the body weight of the pregnant mice from around 2-3 days after administration until the end of gestation. The greatest effects were evident when the BPA was given during the later stages of pregnancy, and with higher doses. They also showed marked reduction in food intake and, to a lesser extent, in water intake. Furthermore, doses of BPA induced a reduction in implantation sites, lower foetal body weight and increased mortality rates. Abortion and foetal resorption rates were not affected by BPA administration, however. The above findings were concluded by discussing the possible mechanisms involved in producing these effects.

Identification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb.

Houttuynia cordata Thunb., a perennial herb belonging to the Saururaceae family is a well-known ingredient of Traditional Chinese medicine (TCM) with several therapeutic properties. During the severe acute respiratory syndrome (SARS) outbreak in China, it was one of the approved ingredients in SARS preventative formulations and therefore, the plant may contain novel bioactive chemicals that can be used to suppress the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus for which there are currently no effective drugs available. Like all RNA viruses, SARS-CoV-2 encode RNA-dependent RNA polymerase (RdRp) enzyme which aids viral gene transcription and replication. The present study is aimed at understanding the potential of bioactive compounds from H. cordata as inhibitors of the SARS-CoV-2 RdRp enzyme. We investigated the drug-likeness of the plant's active constituents, such as alkaloids, polyphenols, and flavonoids, as well as their binding affinity for the RdRp enzyme. Molecular docking experiments show that compounds 3 (1,2,3,4,5-pentamethoxy-dibenzo-quinolin-7-one), 14 (7-oxodehydroasimilobine), and 21 (1,2-dimethoxy-3-hydroxy-5-oxonoraporphine) have a high affinity for the drug target and that the complexes are maintained by hydrogen bonds with residues like Arg553, Cys622 and Asp623, as well as hydrophobic interactions with other residues. The lead compounds' complexes with the target enzyme remained stable throughout the molecular dynamics simulation. Analysis of molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA) revealed the key residues contributing considerably to binding free energy. Thus, the findings reveal the potential of H. cordata bioactive compounds as anti-SARS-CoV-2 drug candidate molecules against the target enzyme.

A novel biocompatible formate bridged 1D-Cu(ii) coordination polymer induces apoptosis selectively in human lung adenocarcinoma (A549) cells.

Copper compounds are promising candidates for next-generation metal anticancer drugs. Therefore, we synthesized and characterized a formate bridged 1D coordination polymer [Cu(L)(HCOO)2]n, (L = 2-methoxy-6-methyl-3-((quinolin-8-ylimino)methyl)chroman-4-ol), PCU1, wherein the Cu(ii) center adopts a square pyramidal coordination environment with adjacent CuCu distances of 5.28 Å. Primarily, in vitro DNA interaction studies revealed a metallopolymer which possesses high DNA binding propensity and cleaves DNA via the oxidative pathway. We further analysed its potential on cancerous cells MCF-7, HeLa, A549, and two non-tumorigenic cells HEK293 and HBE. The selective cytotoxicity potential of PCU1 against A549 cells driven us to examine the mechanistic pathways comprehensively by carrying out various assays viz, cell cycle arrest, Annexin V-FTIC/PI assay, autophagy, intercellular localization, mitochondrial membrane potential 'MMP', antiproliferative assay, and gene expression of TGF-ß and MMP-2.

Structure-based virtual screening of phytochemicals and repurposing of FDA approved antiviral drugs unravels lead molecules as potential inhibitors of coronavirus 3C-like protease enzyme.

Coronaviruses are enveloped positive-strand RNA viruses belonging to family Coronaviridae and order Nidovirales which cause infections in birds and mammals. Among the human coronaviruses, highly pathogenic ones are Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV) which have been implicated in severe respiratory syndrome in humans. There are no approved antiviral drugs or vaccines for the treatment of human CoV infection to date. The recent outbreak of new coronavirus pandemic, coronavirus disease 2019 (COVID-19) has caused a high mortality rate and infections around the world which necessitates the need for the discovery of novel anti-coronaviral drugs. Among the coronaviruses proteins, 3C-like protease (3CLpro) is an important drug target against coronaviral infection as the auto-cleavage process catalysed by the enzyme is crucial for viral maturation and replication. The present work is aimed at the identification of suitable lead molecules for the inhibition of 3CLpro enzyme via a computational screening of the Food and Drug Administration (FDA) approved antiviral drugs and phytochemicals. Based on binding energies and molecular interaction studies, we shortlisted five lead molecules (both FDA approved drugs and phytochemicals) for each enzyme targets (SARS-CoV-2 3CLpro, SARS-CoV 3CLpro and MERS-CoV 3CLpro). The lead molecules showed higher binding affinity compared to the standard inhibitors and exhibited favourable hydrophobic interactions and a good number of hydrogen bonds with their respective targets. A few promising leads with dual inhibition potential were identified among FDA approved antiviral drugs which include DB13879 (Glecaprevir), DB09102 (Daclatasvir), molecule DB09297 (Paritaprevir) and DB01072 (Atazanavir). Among the phytochemicals, 11,646,359 (Vincapusine), 120,716 (Alloyohimbine) and 10,308,017 (Gummadiol) showed triple inhibition potential against all the three targets and 102,004,710 (18-Hydroxy-3-epi-alpha-yohimbine) exhibited dual inhibition potential. Hence, the proposed lead molecules from our findings can be further investigated through in vitro and in vivo studies to develop into potential drug candidates against human coronaviral infections.

In silico screening of FDA approved drugs reveals ergotamine and dihydroergotamine as potential coronavirus main protease enzyme inhibitors.

Coronaviruses with the largest viral genomes are positive-sense RNA viruses associated with a history of global epidemics such as the severe respiratory syndrome (SARS), the Middle East respiratory syndrome (MERS) and recently the coronavirus disease 2019 (COVID-19). There has been no vaccines or drugs available for the treatment of human coronavirus infections to date. In the present study, we have explored the possibilities of FDA approved drugs as potential inhibitors of the coronavirus main protease, a therapeutically important drug target playing a salient role in the maturation and processing of the viral polyproteins and are vital for viral replication and transcription. We have used molecular docking approach and have successfully identified the best lead molecules for each enzyme target. Interestingly, the anti-migraine drugs such as ergotamine and its derivative, dihydroergotamine were found to bind to all the three target enzymes within the Cys-His catalytic dyad cleft with lower binding energies as compared to the control inhibitors (α-ketoamide 13b, SG85 and GC813) and the molecules are held within the pocket through a good number of hydrogen bonds and hydrophobic interactions. Hence both these lead molecules can be further taken for wet-lab experimentation studies before repurposing them as anti-coronaviral drug candidates.

Evaluation of (ɳ6-p-cymene) ruthenium diclofenac complex as anticancer chemotherapeutic agent: interaction with biomolecules, cytotoxicity assays.

The designing of metal-based anticancer therapeutic agents can be optimized in a better and rapid way if the ligands utilized have standalone properties. Therefore, even when the organometallic/coordination complex (i.e., metallodrug) gets dissociated in extreme conditions, the ligand can endorse its biological properties. Herein, we have synthesized and characterized ɳ6-p-cymene ruthenium diclofenac complex. Furthermore, the ruthenium complex interactions with human serum albumin (HSA) and ct-DNA have been studied using various spectroscopic studies viz., UV, fluorescence, and circular dichroism and exhibited a significant binding propensity. Furthermore, in vitro cytotoxicity assays were carried out against human breast cancer "MCF-7" cell line. The ɳ6-p-cymene ruthenium diclofenac complex registered significant cytotoxicity with an IC50 value of ∼25.0 µM which is comparable to the standard drugs. The ɳ6-p-cymene ruthenium diclofenac complex was able to decrease the MCF-7 cell proliferation and induced significant levels of apoptosis with relatively low toxicity.

The binding proximity of methyl ß-lilacinobioside isolated from Caralluma retrospiciens with topoisomerase II attributes apoptosis in breast cancer cell line.

The alterations in somatic genomes that controls the mechanism of cell division as a main cause of cancer, and then the drug that specifically toxic to the cancer cells further complicates the process of the development of the widely effective potential anticancer drug. The side effects of the drug as well as the radiotherapy used for the treatment of cancer is severe; therefore, the search of the natural products from the sources of wild plants having anticancer potential is become immense importance today. The ethno-medicinal survey undertaken in Al-Fayfa and Wadi-E-Damad region of southern Saudi Arabia revealed that the Caralluma retrospiciens (Ehrenb.) N.E.Br. (family Apocynaceae) is being used for the treatment of cancer by the native inhabitants. The biological evaluation of anticancer potential of bioassay-guided fractionations of methanolic extract of whole plant of C. retrospiciens against human breast adenocarcinoma cell line (MCF-7) followed by characterization using spectroscopic methods confirmed the presence of methyl ß-lilacinobioside, a novel active constituent reported for the first time from C. retrospiciens, is capable of inhibition of cell proliferation and induction of apoptosis in MCF-7 cells by regulating ROS mediated autophagy, and thus validated the folkloric claim. Based on a small-scale computational target screening, Topoisomerase II was identified as the potential binding target of methyl ß-lilacinobioside.

Ovarian development and histological observations of threatened dwarf snakehead fish, Channa gachua (Hamilton, 1822).

Channa gachua were monthly sampled throughout a year and the histological analysis of their ovaries was done to determine the changes occurring in ovarian development. Based on histological examination of the ovaries, the oogenic process of C. gachua undergoes distinct cyclic and seasonal morphological changes. Five different developmental stages were identified under three major categories: pre-spawning (immature, maturing, mature), spawning (ripe-running) and post-spawning (spent). The peak spawning period of C. gachua was noticed during December - February. The gonadosomatic index (GSI) and ova diameter ranged from 0.79 to 3.61% and 543-1123 µm respectively. The highest mean GSI (3.61 ± 0.16) and oocyte diameter (1123 ± 55 µm) were observed in December indicating that during this month the gonadal development reached maturity.