Hallmarks of diabetes mellitus and insights into the therapeutic potential of synergy-based combinations of phytochemicals in reducing oxidative stress-induced diabetic complications.

Diabetes mellitus (DM) is a serious health issue and is still one of the major causes of mortality around the globe. Natural products have progressively integrated into modern, advanced medical practices. Phytoconstituents from some medicinal plants have demonstrated therapeutic activity in treating different metabolic disorders and have been used to treat DM and its severe complications. The present review provides details of the major anti-diabetic targets identified in the literature and also provides comprehensive information regarding the therapeutic role of a synergy-based combination of phytoconstituents that functions by controlling specific molecular pathways synchronously by inhibiting certain key regulators involved in the development and progression of DM. The review also implicated the role of oxidative stress in diabetic complications and presented scientific validations of phytochemicals and their synergy-based combination using in vitro and or in vivo approaches.

Graphene quantum dot-crafted nanocomposites: shaping the future landscape of biomedical advances.

Graphene quantum dots (GQDs) are a newly developed class of material, known as zero-dimensional nanomaterials, with characteristics derived from both carbon dots (CDs) and graphene. GQDs exhibit several ideal properties, including the potential to absorb incident energy, high water solubility, tunable photoluminescence, good stability, high drug-loading capacity, and notable biocompatibility, which make them powerful tools for various applications in the field of biomedicine. Additionally, GQDs can be incorporated with additional materials to develop nanocomposites with exceptional qualities and enriched functionalities. Inspired by the intriguing scientific discoveries and substantial contributions of GQDs to the field of biomedicine, we present a broad overview of recent advancements in GQDs-based nanocomposites for biomedical applications. The review first outlines the latest synthesis and classification of GQDs nanocomposite and enables their use in advanced composite materials for biomedicine. Furthermore, the systematic study of the biomedical applications for GQDs-based nanocomposites of drug delivery, biosensing, photothermal, photodynamic and combination therapies are emphasized. Finally, possibilities, challenges, and paths are highlighted to encourage additional research, which will lead to new therapeutics and global healthcare improvements.

New reports of pathogen spectrum associated with bulb rot and their interactions during the development of rot in tulip.

Bulb rot, a highly damaging disease of tulip plants, has hindered their profitable cultivation worldwide. This rot occurs in both field and storage conditions posing significant challenges. While this disease has been attributed to a range of pathogens, previous investigations have solely examined it within the framework of a single-pathogen disease model. Our study took a different approach and identified four pathogens associated with the disease: Fusarium solani, Penicillium chrysogenum, Botrytis tulipae, and Aspergillus niger. The primary objective of our research was to examine the impact of co-infections on the overall virulence dynamics of these pathogens. Through co-inoculation experiments on potato dextrose agar, we delineated three primary interaction patterns: antibiosis, deadlock, and merging. In vitro trials involving individual pathogen inoculations on tulip bulbs revealed that B. tulipae,was the most virulent and induced complete bulb decay. Nonetheless, when these pathogens were simultaneously introduced in various combinations, outcomes ranged from partial bulb decay to elongated rotting periods. This indicated a notable degree of antagonistic behaviour among the pathogens. While synergistic interactions were evident in a few combinations, antagonism overwhelmingly prevailed. The complex interplay of these pathogens during co-infection led to a noticeable change in the overall severity of the disease. This underscores the significance of pathogen-pathogen interactions in the realm of plant pathology, opening new insights for understanding and managing tulip bulb rot.

Axial compression tests on CFRP strengthened CFS plain angle short columns.

A comprehensive test program was performed to experimentally investigate the effect of CFRP strengthening on the axial strength and stability of CFS plain angle short columns subjected to monotonic axial compression. A total of 28 specimens were tested by varying the CFRP strengthening configurations for different column heights. Both uni-directional (CF_UD) and bi-directional (CF_BD) CFRP were considered. The influence of various parameters such as the type of CFRP, fiber orientation, and number of CFRP layers was investigated and discussed in detail. For single layer (ply) of CFRP, CF_UD-0° strengthening configuration resulted in maximum increase of axial capacity by 58.33% and 45.72% (in comparison to bare steel specimens), corresponding to 0.5 m and 1.0 m column lengths respectively. All the bare steel and skin-strengthened specimens failed predominantly due to torsional-flexural buckling mode. Additional layer of CFRP wrapping was found to enhance the axial capacity further and CF_UD-0°/BD was found to possess greater capacity in the case of double layer of CFRP. Adopting cardboard in-fill in addition to CF_UD-0° wrap has prevented the torsional mode of buckling and resulted in a peak increase of axial capacity by 192.55% and 240.61% corresponding to 500 mm and 100 mm long specimens, respectively.

Adoption of hooped-battens in cold-formed steel built-up columns for superior axial performance.

Previous research on cold-formed steel (CFS) battened columns has identified the critical factors influencing their performance and accordingly, their limiting values for improved performance have been recommended. However, these studies involved connecting battens to the chords (channels) via their flanges, leaving the slenderest component disconnected from the web. This study introduces a novel hooped-batten (tubular-element) that links both webs and flanges of the chords together, thereby improving the structural integrity of the built-up system and curtailing the half-wave buckling length in the webs. As a result, axial strength and stability in these built-up columns may improve adequately. Firstly, a numerical model of a conventional CFS battened column was developed in ABAQUS and verified against test results on the same reported in literature. Afterward, the validated model was used to simulate the behaviour of CFS built-up columns with hooped-battens. Two key parameters i.e., unbraced chord slenderness and overall column slenderness were varied to explore their influence on the axial behaviour of built-up columns in terms of peak strengths, failure modes and load-displacement characteristics. The performance of the hooped-battened columns was compared with the identical conventional battened columns, which reflects that the former exhibits superior strength and stability characteristics over the latter.

Development of tubulin polymerization inhibitors as anticancer agents.

INTRODUCTION: Microtubules are intracellular, filamentous, polymeric structures that extend throughout the cytoplasm, composed of α-tubulin and ß-tubulin subunits. They regulate many cellular functions including cell polarity, cell shape, mitosis, intracellular transport, cell signaling, gene expression, cell integrity, and are associated with tumorigenesis. Inhibition of tubulin polymerization within tumor cells represents a crucial focus in the pursuit of developing anticancer treatments. AREAS COVERED: This review focuses on the natural product and their synthetic congeners as tubulin inhibitors along with their site of interaction on tubulin. This review also covers the developed novel tubulin inhibitors and important patents focusing on the development of tubulin inhibition for cancer treatment reported from 2018 to 2023. The scientific and patent literature has been searched on PubMed, Espacenet, ScienceDirect, and Patent Guru from 2018-2023. EXPERT OPINION: Tubulin is one of the promising targets explored extensively for drug discovery. Compounds binding in the colchicine site could be given importance because they can elude resistance mediated by the P-glycoprotein efflux pump and no colchicine site binding inhibitor is approved by FDA so far. The research on the development of antibody drug conjugates (ADCs) for tubluin polymerization inhibition could be significant strategy for cancer treatment.

Immunohistochemical expression of E-Cadherin and Cyclin D1 in different grades of oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, representing up to 80-90% of all malignant neoplasms of the oral cavity. It results from the multistep accumulation of heterogeneous genetic changes. Important risk factors for OSCC include the use of tobacco or betel quid chewing, alcohol consumption, human papillomavirus and poor nutrition. E-Cadherin as a tumour suppressor gene sets a threshold for Wnt/ß-catenin signalling. When expression of E-Cadherin is lost, potentiation of Wnt signalling pathway occurs leading to loss of cell-cell adhesion. The cyclin D1 gene (CCND1) located on chromosome 11q13 encodes a nuclear protein that is the regulatory subunit of Cdk-4 and Cdk-6. Cyclin D1 plays a major role in cell cycle transition from G1 to S phase by contributing to inactivation of the retinoblastoma gene product, and overexpression of CCND1 has been reported in 35-40% cases of OSCC. Aim: Considering this, we decided to evaluate and compare the expression of CE-Cadherin and Cyclin D1 in different grades of OSCC. Materials and Methods: A retrospective study was carried out on 60 formalin-fixed paraffin embedded tissue blocks comprising of 20 cases of well-differentiated OSCC, 20 cases of moderately differentiated OSCC and 20 cases of poorly differentiated OSCC. Diagnosed (using H and E), with oral mucosa taken as control. Results: There was downregulation of E-Cadherin and overexpression of Cyclin D1 in increasing grades of OSCC and the difference was statistically significant. E-Cadherin was localised to membranous and shifted to cytoplasm as the grade worsened. Cyclin D1 was localised to nuclei of cells and the expression was seen more at the peripheral portions of tumour islands depicting the proliferative activity of tumour front. Conclusion: The study revealed a good prognostic role of both E-Cadherin and Cyclin D1 in OSCC. The markers can be used for prognostic as well as therapeutic purposes.

Phytochemistry and Pharmacological Activity of Malva sylvestris L: A Detailed Insight.

Malva sylvestris L., is commonly referred to as Mallow and is found in Europe, Asia and Africa. This has been traditionally used for inflammation, gastrointestinal disturbances, skin disorders, menstrual pains, and urological disorders. This review covers phytoconstituents and Pharmacological activities of M. sylvestris. The plant contains a large number of phytochemical constituents having diverse pharmacological activities. The plant contains many phenolic compounds responsible for its strong antioxidant activity. Coumarins from Mallow have a potential anticancer activity. Malva sylvestris also contains essential as well as non-essential elements and minerals. Many researchers have provided evidence that Malva sylvestris is a good candidate for use as a medicinal herb and has good nutritional value. The leaves, in particular, offer properties like anticancer, skin whitening, and anti-aging. Furthermore, the aqueous extract was recently shown to have an anti-ulcerogenic effect. Malva sylvestris has a high potential for use in cosmetics such as skin whitening and anti-aging treatments. Methanolic extracts of Malva sylvestris leaves, and flowers showed strong antibacterial activity against a common plant pathogen bacterium. The plant also contains Malvone A, which is responsible for antibacterial action. The plant also possesses anti-inflammatory, analgesic, wound healing properties and various other activities.

Characterization of Pre-Breeding Wheat (Triticum aestivum L.) Germplasm for Stripe Rust Resistance Using Field Phenotyping and Genotyping.

Wheat is highly affected by stripe rust disease, particularly under cooler environments, and the losses can reach up to 100 percent depending on the intensity of infection and the susceptibility of the genotype. The most effective method to manage this disease is the use of resistant varieties. In the present study, 192 wheat genotypes were evaluated for stripe rust resistance under field conditions and also in a laboratory using molecular markers. These lines included pre-breeding germplasm developed for rust resistance and some high-yielding commercially grown wheat varieties. Out of 192 genotypes, 53 were found to be resistant, and 29 showed moderate resistance reaction under field conditions, whereas the remaining genotypes were all either moderately susceptible or susceptible. Under controlled conditions, out of 109 genotypes, only 12 were found to be resistant to all the six virulent/pathogenic pathotypes. Additionally, a selection of 97 genotypes were found resistant in field screening and were subjected to molecular validation using the markers linked to major R-genes, viz., Yr5, Yr10, Yr15 and Yr17. Nine genotypes possessed the Yr5 gene, twelve had the Yr10 gene, fourteen had the Yr15 gene and thirty-two had the Yr17 gene. The resistance genes studied in the current study are effective in conferring resistance against stripe rust disease. The genotypes identified as resistant under both field and controlled conditions can be used as sources in stripe rust resistance breeding programs.

Photothermal therapy using graphene quantum dots.

The rapid development of powerful anti-oncology medicines have been possible because of advances in nanomedicine. Photothermal therapy (PTT) is a type of treatment wherein nanomaterials absorb the laser energy and convert it into localized heat, thereby causing apoptosis and tumor eradication. PTT is more precise, less hazardous, and easy-to-control in comparison to other interventions such as chemotherapy, photodynamic therapy, and radiation therapy. Over the past decade, various nanomaterials for PTT applications have been reviewed; however, a comprehensive study of graphene quantum dots (GQDs) has been scantly reported. GQDs have received huge attention in healthcare technologies owing to their various excellent properties, such as high water solubility, chemical stability, good biocompatibility, and low toxicity. Motivated by the fascinating scientific discoveries and promising contributions of GQDs to the field of biomedicine, we present a comprehensive overview of recent progress in GQDs for PTT. This review summarizes the properties and synthesis strategies of GQDs including top-down and bottom-up approaches followed by their applications in PTT (alone and in combination with other treatment modalities such as chemotherapy, photodynamic therapy, immunotherapy, and radiotherapy). Furthermore, we also focus on the systematic study of in vitro and in vivo toxicities of GQDs triggered by PTT. Moreover, an overview of PTT along with the synergetic application used with GQDs for tumor eradication are discussed in detail. Finally, directions, possibilities, and limitations are described to encourage more research, which will lead to new treatments and better health care and bring people closer to the peak of human well-being.

Inhibition of Autophagy and the Cytoprotective Role of Smac Mimetic against ROS-Induced Cancer: A Potential Therapeutic Strategy in Relapse and Chemoresistance Cases in Breast Cancer.

With more than a million deaths each year, breast cancer is the top cause of death in women. Around 70% of breast cancers are hormonally responsive. Although several therapeutic options exist, cancer resistance and recurrence render them inefficient and insufficient. The major key reason behind this is the failure in the regulation of the cell death mechanism. In addition, ROS was also found to play a major role in this problem. The therapeutic benefits of Smac mimetic compound (SMC) BV6 on MCF7 were examined in the current study. Treatment with BV6 reduces viability and induces apoptosis in MCF7 breast cancer cells. BV6 suppresses autophagy and has demonstrated a defensive role in cancer cells against oxidative stress caused by H2O2. Overall, the present investigation shows that SMC has therapeutic and cytoprotective potential against oxidative stress in cancer cells. These Smac mimetic compounds may be used as anti-cancer drugs as well as antioxidants alone or in conjunction with other commonly used antioxidants.

Genetic footprint of population diversity and genetic structure of Venturia inaequalis infecting apple (Malus × domestica Borkh.).

Apple scab instigated by Venturia inaequalis impels remarkable losses to apple fruit production. In an effort to comprehend the key mechanisms of evolutionary potential defining V. inaequalis population, 132 isolates of V. inaequalis from five commercial apple orchards were collected and assayed using 14 microsatellite markers. The average diversity was observed within the individuals of populations based on the Shannon-Wieners index (I) and observed heterozygosity (Ho) was average but considerably lower than expected heterozygosity (He). The genetic differentiation based on FST values was revealed as an average measure of divergence between populations and had varying proportions of gene flow and migration among themselves. Analysis of Molecular Variance (AMOVA) revealed that variance (94%) was dispersed across individuals with a significant (6%) variation between populations from different regions. To examine host specialization within the V. inaequalis population, the assignment approach based on K-means of clustering (an unsupervised machine learning approach), revealed that the clustering method supported three clusters at (K = 3) and three major clusters were also observed in Principle Component Analysis (PCA). Additionally, Nei's genetic distance values, pairwise estimates of genetic differentiation, dendrogram using the neighbor-joining and PCoA revealed the random distribution of V. Inaequalis isolates that depicted a high proportion of genotypic diversity within populations and population genetic structure. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03672-2.

Metal complexes of xanthine and its derivatives: Synthesis and biological activity.

Xanthine and its derivatives are considered an important class of N-heterocyclic purine compounds that have gained significant importance in medicinal chemistry. N-heterocyclic carbene (NHC) and N-coordinated metal complexes of xanthine and its derivatives have revealed a range of new possibilities for their use as therapeutic agents in addition to their established catalytic behavior. The metal complexes of xanthine and its derivatives have been designed and synthesized for the exploration of their potential therapeutic applications. These metal complexes based on the xanthine scaffold exhibited various potential medicinal applications including anticancer, antibacterial, and antileishmanial activity. The metal complexes of xanthine and its derivatives shall pave the way for the rational design and development of new therapeutic agents. In the present comprehensive review, we highlighted the recent advancements in the synthesis and medicinal applications of metal complexes based on N-heterocyclic carbene (NHC) derived from xanthine scaffolds.

Drug Standardization through Pharmacognostic Approaches and Estimation of Anticancer Potential of Chamomile (Matricaria chamomilla L.) using Prostate-Cancer cell lines: An In-vitro Study.

Cancer is the major challenge across world and the adenocarcinoma of prostate malignancy is the second most prevalent male cancer. Various medicinal plants are used for the treatment and management of various cancers. Matricaria chamomilla L., is one of the extensively used Unani medicament for the treatment of various type of diseases. In the current study we evaluated most of the parameters prescribed for drug standardization using pharmacognostic approaches. The 2,2 Diphenyl-1-picryl hydrazyl (DPPH) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla. Moreover, we analyzed the antioxidant and cytotoxic activity of M. chamomilla (Gul-e Babuna) through in-vitro method. DPPH (2,2-diphenyl-1-picryl-hydrazl-hydrate) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla. CFU and wound healing assay were performed to determine the anti-cancer activity. The results demonstrated that various extracts of M. chamomilla fulfilled most of the parameters of drug standardization and contained good antioxidant and anticancer activities. The ethyl acetate showed higher anticancer activity followed by aqueous, hydroalcoholic, petroleum benzene and methanol by CFU method. Also, the wound healing assay demonstrated that ethyl acetate extract has more significant effect followed by methanol and petroleum benzene extract on prostate cancer cell line (C4-2). The current study concluded that the extract of M. chamomilla flowers could act as good source of natural anti-cancer compounds.

In Silico Analysis of PTP1B Inhibitors and TLC-MS Bioautography-Based Identification of Free Radical Scavenging and α-Amylase Inhibitory Compounds from Heartwood Extract of Pterocarpus marsupium.

Type 2 diabetes mellitus leads to metabolic impairment caused by insulin resistance and hyperglycemia, giving rise to chronic diabetic complications and poor disease prognosis. The heartwood of Pterocarpus marsupium has been used in Ayurveda for a long time, and we sought to find the actual mechanism(s) driving its antidiabetic potential. Methanol was used to prepare the extract using a Soxhlet extraction, and the identification of metabolites was performed by thin-layer chromatography (TLC) and ultraperformance-liquid chromatography and mass spectroscopy (UP-LCMS). The antioxidant potential of methanolic heartwood extract of Pterocarpus marsupium MHPM was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and a reducing power assay. The α-amylase and α-glucosidase enzyme inhibitory potential of MHPM were investigated for their antidiabetic activity against acarbose. TLC-MS-bioautography was performed to identify the compounds responsible for possible antioxidant and antidiabetic activities. Moreover, targeting protein tyrosine phosphatase 1B (PTP1B), a key regulator of insulin resistance, by identified metabolites from MHPM through molecular docking and all-atom molecular dynamics (MD) simulations was also undertaken, suggesting its potential as an antidiabetic herb. The IC50 of free-radical scavenging activity of MHPM against DPPH was 156.342 ± 10.70 µg/mL. Further, the IC50 values of MHPM in α-amylase and α-glucosidase enzymatic inhibitions were 158.663 ± 10.986 µg/mL and 180.21 ± 11.35 µg/mL, respectively. TLC-MS-bioautography identified four free radical scavenging metabolites, and vanillic acid identified by MS analysis showed both free radical scavenging activity and α-amylase inhibitory activity. Among the identified metabolites from MHPM, epicatechin showed significant PTP1B docking interactions, and its MD simulations revealed that PTP1B forms a stable protein-ligand complex with epicatechin throughout the progression, which indicates that epicatechin may be used as a promising scaffold in the development of the antidiabetic drug after isolation from Pterocarpus marsupium. Overall, these findings imply that Pterocarpus marsupium is a source of valuable metabolites that are accountable for its antioxidant and antidiabetic properties.

Medicaid's Moment for Protecting and Promoting Women's Health.

This Viewpoint examines pathways that advocates, policy makers, states, and Medicaid agencies can take to identify opportunities for state Medicaid agencies to protect and promote perinatal health.

Heartwood Extract of Pterocarpus marsupium Roxb. Offers Defense against Oxyradicals and Improves Glucose Uptake in HepG2 Cells.

Diabetes mellitus leads to cellular damage and causes apoptosis by oxidative stress. Heartwood extract of Pterocarpus marsupium has been used in Ayurveda to treat various diseases such as leprosy, diabetes, asthma, and bronchitis. In this study, we worked out the mechanism of the antidiabetic potential of methanolic heartwood extract of Pterocarpus marsupium (MPME). First, metabolic profiling of MPME was done using gas chromatography-mass spectrometry (GCMS), ultra-performance liquid chromatography-mass spectroscopy (UPLC-MS), and high-performance thin-layer chromatography (HPTLC) to identify phenols, flavonoids, and terpenoids in MPME. Biological studies were carried out in vitro using the HepG2 cell line. Many antidiabetic compounds were identified including Quercetin. Methanolic extract of MPME (23.43 µg/mL-93.75 µg/mL) was found to be safe and effective in reducing oxyradicals in HepG2 cells. A concentration of 93.75 µg/mL improved glucose uptake efficiently. A significant decrease in oxidative stress, cell damage, and apoptosis was found in MPME-treated HepG2 cells. The study suggests that the heartwood of Pterocarpus marsupium offers good defense in HepG2 cells against oxidative stress and improves glucose uptake. The results show the significant antidiabetic potential of MPME using a HepG2 cell model. The effect seems to occur by reducing oxidative stress and sensitizing the cells towards glucose uptake, hence lowering systemic glucose levels, as well as rescuing ROS generation.