Morpho-physiological growth performance and phytoremediation capabilities of selected xerophyte grass species toward Cr and Pb stress

Being sessile organisms, plants cannot escape unwanted changes in the environment. The rapid human population explosion caused significant environmental problems. Heavy metals produced through various sources can cause severe damage to living organisms. The study was planned to evaluate four grass species’ morpho-physiological growth characteristics and phytoremediation capabilities under chromium (Cr) and lead stress (Pb) in the arid climate. Typha angustifolia, Tragus roxburghii, Aeluropus logopoides, and Cenchrus ciliaris grass species were used for the study. One-year-old stubbles from the Cholistan desert were used for the experiment. Cr treatments in the form of K2Cr2O7 were applied at 0, 20, 40, and 80 mg L–1, whereas Pb was applied as PbCl2 at 0, 50, 200, and 500 mg L–1 as control, low, moderate and high-stress, respectively. After 6 weeks of heavy metals treatments, plants were harvested and analyzed for growth performance and phytoremediation capabilities. Results depicted that, regarding morphological attributes, T. angustifolia performed better, followed by C. ciliaris; no clear pattern was observed for T. roxburghii and A. logopoides. The CO2 assimilation rate (Co2d) and water use efficiency (WUE) increased as the heavy metal stress increased in all species under both metals. In contrast, total chlorophyll content was higher under low stress. Other physiological parameters, such as relative humidity (RHd), net photosynthetic rate (A), transpiration rate (E), stomatal conductance (Gs), leaf internal CO2 concentration (Ci) and membrane stability index (MSI) gradually decreased as the Cr, and Pb stress levels increased among all the species. Moreover, Cr and Pb absorption contents of T. angustifolia were higher than the other three species at each stress level. Overall, T. angustifolia thrived against heavy metals stress and showed higher biomass, maximum photosynthetic measurements, WUE and higher metal absorption among all the selected species. Results concluded that although all the selected species behaved fine under stress conditions, T. angustifolia performance was better; thus, it can be used to remediate the soil near industrial estates

Navigating bioactivity space in anti-tubercular drug discovery through the deployment of advanced machine learning models and cheminformatics tools : a molecular modeling based retrospective study

Mycobacterium tuberculosis is the bacterial strain that causes tuberculosis (TB). However, multidrug-resistant and extensively drug-resistant tuberculosis are significant obstacles to effective treatment. As a result, novel therapies against various strains of M. tuberculosis have been developed. Drug development is a lengthy procedure that includes identifying target protein and isolation, preclinical testing of the drug, and various phases of a clinical trial, etc., can take decades for a molecule to reach the market. Computational approaches such as QSAR, molecular docking techniques, and pharmacophore modeling have aided drug development. In this review article, we have discussed the various techniques in tuberculosis drug discovery by briefly introducing them and their importance. Also, the different databases, methods, approaches, and software used in conducting QSAR, pharmacophore modeling, and molecular docking have been discussed. The other targets targeted by these techniques in tuberculosis drug discovery have also been discussed, with important molecules discovered using these computational approaches. This review article also presents the list of drugs in a clinical trial for tuberculosis found drugs. Finally, we concluded with the challenges and future perspectives of these techniques in drug discovery.Peer reviewe

Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases

Neurodegenerative diseases are a serious and widespread global public health burden amongst aging populations. The total estimated worldwide global cost of dementia was US$818 billion in 2015 and has been projected to rise to 2 trillion US$ by 2030. While advances have been made to understand different neurodegenerative disease mechanisms, effective therapeutic strategies do not generally exist. Several drugs have been proposed in the last two decades for the treatment of different types of neurodegenerative diseases, with little therapeutic benefit, and often with severe adverse and side effects. Thus, the search for novel drugs with higher efficacy and fewer drawbacks is an ongoing challenge in the treatment of neurodegenerative disease. Several natural compounds including polysaccharides have demonstrated neuroprotective and even therapeutic effects. Natural polysaccharides are widely distributed in plants, animals, algae, bacterial and fungal species, and have received considerable attention for their wide-ranging bioactivity, including their antioxidant, anti-neuroinflammatory, anticholinesterase and anti-amyloidogenic effects. In this review, we summarize different mechanisms involved in neurodegenerative diseases and the neuroprotective effects of natural polysaccharides, highlighting their potential role in the prevention and therapy of neurodegenerative disease

PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment

PD-1 (Programmed Cell Death Protein-1) and PD-L1 (Programmed Cell Death Ligand-1) play a crucial role in regulating the immune system and preventing autoimmunity. Cancer cells can manipulate this system, allowing them to escape immune detection and promote tumor growth. Therapies targeting the PD-1/PD-L1 pathway have transformed cancer treatment and have demonstrated significant effectiveness against various cancer types. This study delves into the structure and signaling dynamics of PD-1 and its ligands PD-L1/PD-L2, the diverse PD-1/PD-L1 inhibitors and their efficacy, and the resistance observed in some patients. Furthermore, this study explored the challenges associated with the PD-1/PD-L1 inhibitor treatment approach. Recent advancements in the combination of immunotherapy with chemotherapy, radiation, and surgical procedures to enhance patient outcomes have also been highlighted. Overall, this study offers an in-depth overview of the significance of PD-1/PD-L1 in cancer immunotherapy and its future implications in oncology

Medicinal Plants as Therapeutic Alternatives to Combat Mycobacterium tuberculosis : A Comprehensive Review

Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (MTB) and a significant health concern worldwide. The main threat to the elimination of TB is the development of resistance by MTB to the currently used antibiotics and more extended treatment methods, which is a massive burden on the health care system. As a result, there is an urgent need to identify new, effective therapeutic strategies with fewer adverse effects. The traditional medicines found in South Asia and Africa have a reservoir of medicinal plants and plant-based compounds that are considered another reliable option for human beings to treat various diseases. Abundant research is available for the biotherapeutic potential of naturally occurring compounds in various diseases but has been lagging in the area of TB. Plant-based compounds, or phytoproducts, are being investigated as potential anti-mycobacterial agents by reducing bacterial burden or modulating the immune system, thereby minimizing adverse effects. The efficacy of these phytochemicals has been evaluated through drug delivery using nanoformulations. This review aims to emphasize the value of anti-TB compounds derived from plants and provide a summary of current research on phytochemicals with potential anti-mycobacterial activity against MTB. This article aims to inform readers about the numerous potential herbal treatment options available for combatting TB.publishedVersionPeer reviewe

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

REST Controls Self-Renewal and Tumorigenic Competence of Human Glioblastoma Cells

The Repressor Element 1 Silencing Transcription factor (REST/NRSF) is a master repressor of neuronal programs in non-neuronal lineages shown to function as a central regulator of developmental programs and stem cell physiology. Aberrant REST function has been associated with a number of pathological conditions. In cancer biology, REST has been shown to play a tumor suppressor activity in epithelial cancers but an oncogenic role in brain childhood malignancies such as neuroblastoma and medulloblastoma. Here we examined REST expression in human glioblastoma multiforme (GBM) specimens and its role in GBM cells carrying self-renewal and tumorigenic competence. We found REST to be expressed in GBM specimens, its presence being particularly enriched in tumor cells in the perivascular compartment. Significantly, REST is highly expressed in self-renewing tumorigenic-competent GBM cells and its knock down strongly reduces their self-renewal in vitro and tumor-initiating capacity in vivo and affects levels of miR-124 and its downstream targets. These results indicate that REST contributes to GBM maintenance by affecting its self-renewing and tumorigenic cellular component and that, hence, a better understanding of these circuitries in these cells might lead to new exploitable therapeutic targets

International Consortium on Mammographic Density:methodology and population diversity captured across 22 countries

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses

Mammographic density and ageing:A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction

Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study

Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p<00001), age 70 years or older versus younger than 70 years (230 [165-322], p<00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p<00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research