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Introduction: Glioblastoma, which affects a large number of patients every year and has an average overall lifespan of around 14.6 months following diagnosis stands out as the most lethal primary invasive brain tumor. Currently, surgery, radiation, and chemotherapy with temozolomide (TMZ) are the three major clinical treatment approaches. However, the ability to treat patients effectively is usually limited by TMZ resistance. Naringin, a bioflavonoid with anti-cancer, antioxidant, metal-chelating, and lipid-lowering effects, has emerged as a promising therapeutic option. Methods: To explore the targets and pathways of naringin and TMZ in glioblastoma network pharmacology, cell line-based ELISA, flow cytometry, immunocytochemistry, western blotting, and LC-HRMS based metabolomics study were used. Results: The findings through the network pharmacology suggested that the key targets of naringin in the chemosensitization of glioblastoma would be Poly [ADP-ribose] polymerase 1 (PARP-1), O-6-Methylguanine-DNA Methyltransferase (MGMT), and caspases. The functional enrichment analysis revealed that these targets were significantly enriched in important pathways such as p53 signaling, apoptosis, and DNA sensing. Further, the results of the in-vitro study in U87-MG and T98-G glioblastoma cells demonstrated that TMZ and naringin together significantly reduced the percentage of viability and inhibited the DNA repair enzymes PARP-1 and MGMT, and PI3K/AKT which led to chemosensitization and, in turn, induced apoptosis, which was indicated by increased p53, caspase-3 expression and decreased Bcl2 expression. Additionally, a metabolomics study in T98-G glioblastoma cells using liquid chromatography high-resolution mass spectrometry (LC-HRMS) revealed downregulation of C8-Carnitine (-2.79), L-Hexanoylcarnitine (-4.46), DLCarnitine (-2.46), Acetyl-L-carnitine (-3.12), Adenine (-1.3), Choline (-2.07), Propionylcarnitine (-1.69), Creatine (-1.33), Adenosine (-0.84), Spermine (-1.42), and upregulation of Palmitic Acid (+1.03) and Sphingosine (+0.89) in the naringin and TMZ treatment groups. Discussion: In conclusion, it can be said that naringin in combination with TMZ chemosensitized TMZ antiglioma response and induced apoptosis in tumor cells. [ABSTRACT FROM AUTHOR]

Transparent wood composite (TWC) is a novel wood-based polymer composite that combines high optical transmittance (more than 80%) with good mechanical and thermal properties. It offers numerous potential areas of applications, including smart windows, energy-efficient elements, display panels, light diffusers and substrates for solar cells. The sensitivity of TWC towards moisture and biological agents such as fungus becomes important for certain applications. In this study, TWCs were prepared using wood veneers of Populus deltoides (poplar) and Melia dubia (melia) through the process of lignin-modification bleaching and epoxy-resin infiltration. Water-absorption studies were carried out by immersing TWC specimens in deionized water for a duration of 400 h and by exposing specimens to different relative humidity (RH) conditions. The fungal resistance was evaluated by exposing specimens to a brown rot (Oligoporous placentus) and a white rot (Trametes hirsutu) fungus. Results indicated that TWC can absorb a maximum of 8% to 10% of water during a water immersion test for a period of 400 h. Exposing TWC specimens to different RH conditions resulted in no significant moisture adsorption. TWC was highly resistant to white rot and brown rot fungus. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor. The current treatment for GBM includes adjuvant chemotherapy with temozolomide (TMZ), radiation therapy, and surgical tumor excision. There is still an issue because 50% of patients with GBM who get TMZ have low survival rates due to TMZ resistance. The activation of several DNA repair mechanisms, such as Base Excision Repair (BER), DNA Mismatch Repair (MMR), and O-6- Methylguanine-DNA Methyltransferase (MGMT), is the main mechanism via which TMZ resistance develops. The zinc-finger DNA-binding enzyme poly (ADP-ribose) polymerase-1 (PARP1), which is activated by binding to DNA breaks, affects the activation of the MGMT, BER, and MMR pathway deficiency, which results in TMZ resistance in GBM. PARP inhibitors have been studied recently as sensitizing medications to increase TMZ potency. The first member of the PARP inhibitor family to be identified was Olaparib. It inhibits PARP1 and PARP2, which causes apoptosis in cancer cells and DNA strand break. Olaparib is currently investigated as a radio- and/or chemo-sensitizer in addition to being used as a single agent because it may increase the cytotoxic effects of other treatments. This review addresses Olaparib and its significance in treating TMZ resistance in GBM., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The DPP-4 enzyme degrades incretin hormones GLP-1 and GIP. DPP-4 inhibitors are found effective in the prevention of the degradation of incretins. Xanthine scaffold-bearing molecules are reported as potential DPP-4 inhibitors for treating type 2 diabetes mellitus, e.g. the marketed drug linagliptin. In this work, structure-guided alignment-dependent atom- and Gaussian field-based 3D-QSAR have been performed on a dataset of 75 molecules. The robustness and predictive ability of the developed multifacet 3D-QSAR models were validated on different statistical parameters and found to be statistically fit. The favorable and unfavorable pharmacophoric features were mapped for each multifacet 3D-QSAR model based on three alignment sets (1-3). A five-point common pharmacophore hypothesis was generated separately for each set of alignments. The molecular dynamics simulations (up to 100 ns) were performed for the potent molecule from each alignment set (Compounds 12 , 40 and 57 ) compared to reference standard linagliptin to study the binding energy and stability of target-ligand complexes. The MM-PBSA calculations revealed that the binding free energy and stability of compounds 12 (-40.324 ± 17.876 kJ/mol), 40 (-80.543 ± 21.782 kJ/mol) and 57 (-50.202 ± 16.055 kJ/mol) were better than the reference drug linagliptin (-20.390 ± 63.200 kJ/mol). The generated contour maps from structure-guided alignment-dependent multifacet 3D-QSAR models offer information about the structure-activity relationship (SAR) and ligand-target binding energy and stability data from MD simulation may be utilized to design and develop target selective xanthine-based novel DPP-4 inhibitors.Communicated by Ramaswamy H. Sarma.

Background: Uncontrolled cell growth and proliferation, which originate from lung tissue often lead to lung carcinoma and are more likely due to smoking as well as inhaled environmental toxins. It is widely recognized that tumour cells evade the ability of natural programmed death (apoptosis) and facilitates tumour progression and metastasis. Therefore investigating and targeting the apoptosis pathway is being utilized as one of the best approaches for decades., Objective: This review describes the emergence of SMAC mimetic drugs as a treatment approach, its possibilities to synergize the response along with current limitations as well as future perspective therapy for lung cancer., Method: Articles were analysed using search engines and databases namely Pubmed and Scopus., Result: Under cancerous circumstances, the level of Inhibitor of Apoptosis Proteins (IAPs) gets elevated, which suppresses the pathway of programmed cell death, plus supports the proliferation of lung cancer. As it is a major apoptosis regulator, natural drugs that imitate the IAP antagonistic response like SMAC mimetic agents/Diablo have been identified to trigger cell death. SMAC i.e. second mitochondria activators of caspases is a molecule produced by mitochondria, stimulates apoptosis by neutralizing/inhibiting IAP and prevents its potential responsible for the activation of caspases. Various preclinical data have proven that these agents elicit the death of lung tumour cells. Apart from inducing apoptosis, these also sensitize the cancer cells toward other effective anticancer approaches like chemo, radio, or immunotherapies. There are many SMAC mimetic agents such as birinapant, BV-6, LCL161, and JP 1201, which have been identified for diagnosis as well as treatment purposes in lung cancer and are also under clinical investigation., Conclusion: SMAC mimetics acts in a restorative way in the prevention of lung cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Arsenic is present in above permissible safe limits in groundwater, soil, and food, in various areas of the world. This is increasing exposure to humankind and affecting health in various ways. Alternation in cognition is one among them. Epidemiological research has reflected the impact of arsenic exposure on children in the form of diminished cognition., Aims: Considering this fact, the present study reviewed the impact of arsenic on amyloid precursor protein, which is known to cause one of the commonest cognitive disorders such as Alzheimer's disease., Methods: The present study reviews the arsenic role in the generation of amyloid-beta from its precursor that leads to Alzheimer's disease through the published article from Pubmed and Scopus., Description: According to the findings, regular, long-term exposure to arsenic beginning in infancy changes numerous arsenic level-regulating regions in the rat brain, which are related to cognitive impairments. Arsenic also affects the BBB clearance route by increasing RAGE expression. Arsenic triggers the proamyloidogenic pathway by increasing APP expression and subsequently, its processing by β-secretase and presenilin. Arsenic also affects mitochondrial dynamics, DNA repair pathway and epigenetic changes. The mechanism behind all these changes is explained in the present review article., Conclusion: A raised level of arsenic exposure affects the amyloid precursor protein, a factor for the early precipitation of Alzheimer's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Constipation is one of the most frequent abnormalities of the gastrointestinal system that affects the patient's quality of life. Constipation is more common in women and affects them more frequently as they get older. Many constipated patients take over-the-counter drugs for treatment, but some do not respond to these medicines and need newer, more expensive drugs. Still, many patients are not completely satisfied with these medicines. Unlike other areas, constipation research is not given much importance., Objective: This review discusses targets such as ClC-2, CFTR, opioid receptors, and 5HT-4 receptors, which are important in constipation therapy. The recent focus is also on the gut microbiome with the help of various randomized controlled trials. Pharmacological advances have also added novel targets such as IBAT, PAR-2, and intestinal NHE-3 for constipation treatment., Methods: This review summarises the research on these targets collected from various databases. ClC-2 and CFTR are involved in intestinal chloride secretion followed by sodium or water, which increases stool passage. Non-cancer pain treatment with opioids targeting opiate receptors is considered in 40-90% of patients, which causes constipation as a side effect. On activation, 5HT-4 receptors increase gastrointestinal motility. IBAT is responsible for transporting bile acid into the liver. Bile acid will reach the colon by inhibiting IBAT, stimulating colonic motility, and providing a laxative effect. Activation of the ghrelin receptor results in prokinetic activity in both animals and humans. Intestinal NHE-3 mediates the absorption of Na+ and the secretion of hydrogen into the intestine. Many reports show that PAR-2 is involved in the pathogenesis of gastrointestinal diseases. The gut microbiota influences the peristaltic action of the intestine., Conclusion: Drugs working on these targets positively impact the treatment of constipation, as do the drugs that are currently in clinical trials acting on these targets. The results from the ongoing clinical trials will also provide some valuable information regarding whether these medications will meet the patients' needs in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Due to ineffective diagnosis and analysis, glioblastoma multiforme (GBM), is still the most aggressive form of all cancers. Standard therapy for GBM comprises resection surgery following chemo and radiotherapy, which offers less efficacious treatment to the malignant nature of glioma. Several treatment strategies involving gene therapy, immunotherapy, and angiogenesis inhibition have been employed recently as alternative therapeutics. The main drawback of chemotherapy is resistance, which is mainly due to the enzymes involved in the therapeutic pathways. Our objective is to provide a clear insight into various nano-architectures used in the sensitization of GBM and their importance in drug delivery and bioavailability. This review includes the overview and summary of articles from Pubmed and Scopus search engines. The present era's synthetic and natural drugs used in the treatment of GBM are facing poor Blood Brain Barrier (BBB) permeability issues due to greater particle size. This problem can be resolved by using the nanostructures that showcase high specificity to cross the BBB with their nano-scale size and broader surface area. Nano-architectures act as promising tools for effective brain-targeted drug delivery at a concentration well below the final dose of free drug, thus resulting in safe therapeutic effects and reversal of chemoresistance. The present review focuses on the mechanisms involved in the resistance of glioma cells to chemotherapeutic agents, nano-pharmacokinetics, diverse types of nano-architectures used for potent delivery of the medicine and sensitization in GBM, their recent clinical advances, potential challenges, and future perspective., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)