Terpenoid-Mediated Targeting of STAT3 Signaling in Cancer: An Overview of Preclinical Studies.

Cancer has become one of the most multifaceted and widespread illnesses affecting human health, causing substantial mortality at an alarming rate. After cardiovascular problems, the condition has a high occurrence rate and ranks second in terms of mortality. The development of new drugs has been facilitated by increased research and a deeper understanding of the mechanisms behind the emergence and advancement of the disease. Numerous preclinical and clinical studies have repeatedly demonstrated the protective effects of natural terpenoids against a range of malignancies. Numerous potential bioactive terpenoids have been investigated in natural sources for their chemopreventive and chemoprotective properties. In practically all body cells, the signaling molecule referred to as signal transducer and activator of transcription 3 (STAT3) is widely expressed. Numerous studies have demonstrated that STAT3 regulates its downstream target genes, including Bcl-2, Bcl-xL, cyclin D1, c-Myc, and survivin, to promote the growth of cells, differentiation, cell cycle progression, angiogenesis, and immune suppression in addition to chemotherapy resistance. Researchers viewed STAT3 as a primary target for cancer therapy because of its crucial involvement in cancer formation. This therapy primarily focuses on directly and indirectly preventing the expression of STAT3 in tumor cells. By explicitly targeting STAT3 in both in vitro and in vivo settings, it has been possible to explain the protective effect of terpenoids against malignant cells. In this study, we provide a complete overview of STAT3 signal transduction processes, the involvement of STAT3 in carcinogenesis, and mechanisms related to STAT3 persistent activation. The article also thoroughly summarizes the inhibition of STAT3 signaling by certain terpenoid phytochemicals, which have demonstrated strong efficacy in several preclinical cancer models.

Assessing phytotoxicity and cyto-genotoxicity of two insecticides using a battery of in-vitro biological assays.

Intensive use of chemical pesticides in agriculture poses environmental risks and may have negative impacts on agricultural productivity. The potential phytotoxicity of two chemical pesticides, chlorpyrifos (CPS) and fensulfothion (FSN), were evaluated using Cicer arietinum and Allium cepa as model crops. Different concentrations (0-100 µgmL-1) of both CPS and FSN decreased germination and biological attributes of C. arietinum. High pesticide doses significantly (p ≤ 0.05) caused membrane damage by producing thiobarbituric acid reactive substances (TBARS) and increasing proline (Pro) content. Pesticides elevated ROS levels and substantially increased the superoxide anions and H2O2 concentrations, thus aggravating cell injury. Plants exposed to high pesticide dosages displayed significantly higher antioxidant levels to combat pesticide-induced oxidative stress. Ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) increased by 48%, 93%, 71%, 52% and 94%, respectively, in C. arietinum roots exposed to 100 µgFSNmL-1. Under CLSM, pesticide-exposed C. arietinum and 2',7'-dichlorodihydrofluorescein diacetate (2'7'-DCF) and 3,3'-diaminobenzidine stained roots exhibited increased ROS production in a concentration-dependent manner. Additionally, enhanced Rhodamine 123 (Rhd 123) and Evan's blue fluorescence in roots, as well as changes in mitochondrial membrane potential (ΔΨm) and cellular apoptosis, were both associated with high pesticide dose. Allium cepa chromosomal aberration (CAs) assay showed a clear reduction in mitotic index (MI) and numerous chromosomal anomalies in root meristematic cells. Additionally, a-dose-dependent increase in DNA damage in root meristematic cells of A. cepa and conversion of the super-coiled form of DNA to open circular in pBR322 plasmid revealed the genotoxic potential of pesticides. The application of CPS and FSN suggests phytotoxic and cyto-genotoxic effects that emphasize the importance of careful monitoring of current pesticide level in soil before application and addition at optimal levels to soil-plant system. It is appropriate to prepare both target-specific and slow-release agrochemical formulations for crop protection with concurrent safeguarding of agroecosystems.

Recent advances in the control of volatile organic compounds emissions from indoor wood-based panels: A comprehensive review.

Wood-based panels provide efficient alternatives to materials such as plastics derived from traditional petroleum sources and thereby help to mitigate greenhouse gas emissions. Unfortunately, using indoor manufactured panel products also results in significant emissions of volatile organic compounds including olefins, aromatic and ester compounds, which negatively affect human health. This paper highlights recent developments and notable achievements in the field of indoor hazardous air treatment technologies to guide future research toward environmentally friendly and economically feasible directions that may have a significant impact on the improvement of human settlements. Summarizing and synthesizing the principles, advantages, and limitations of different technologies can assist policymakers and engineers in identifying the most appropriate technology for a particular air pollution control program based on criteria such as cost-effectiveness, efficiency, and environmental impact. In addition, insights into the development of indoor air pollution control technologies are provided and potential areas for innovation, improvement of existing technologies, and development of new technologies are identified. Finally, the authors also hope that this sub-paper will raise public awareness of indoor air pollution issues and promote a better understanding of the importance of indoor air pollution control technologies for public health, environmental protection, and sustainable development.

Remediation and recovery of Kariba weed as emerging contaminant in freshwater and shellfish aquaculture system via solvothermal liquefaction.

Fast growing Kariba weed causes major problems and pollution on freshwater and shellfish aquaculture systems by interfering with nutrient uptake of crops, restricting sunlight penetration, and decreasing water quality due to massive biomass of Kariba weed remnants. Solvothermal liquefaction is considered an emerging thermochemical technique to convert waste into high yield of value-added products. Solvothermal liquefaction (STL) of Kariba weed as an emerging contaminant was performed to investigate the effects of different types of solvents (ethanol and methanol) and Kariba weed mass loadings (2.5-10 % w/v) on treating and reducing the weed via conversion into potentially useful crude oil product and char. Up to 92.53 % of Kariba weed has been reduced via this technique. The optimal conditions for crude oil production were found to be at 5 % w/v of mass loading in methanol medium, resulting in a high heating value (HHV) of 34.66 MJ/kg and yield of 20.86 wt%, whereas the biochar production was found to be optimum at 7.5 % w/v of mass loading in methanol medium, resulting in 29.92 MJ/kg of HHV and 25.38 wt% of yield. The crude oil consisted of beneficial chemical compounds for biofuel production such as hexadecanoic acid, methyl ester (65.02 peak area %) and the biochar showed high carbon content (72.83 %). In conclusion, STL as a remediation for emerging Kariba weed is a feasible process for shellfish aquaculture waste treatment and biofuels production.

Potential medicinal plants to combat viral infections: A way forward to environmental biotechnology.

The viral diseases encouraged scientific community to evaluate the natural antiviral bioactive components rather than protease inhibitors, harmful organic molecules or nucleic acid analogues. For this purpose, medicinal plants have been gaining tremendous importance in the field of attenuating the various kinds of infectious and non-infectious diseases. Most of the commonly used medicines contains the bioactive components/phytoconstituents that are generally extracted from medicinal plants. Moreover, the medicinal plants offer many advantages for the recovery applications of infectious disease especially in viral infections including HIV-1, HIV-2, Enterovirus, Japanese Encephalitis Virus, Hepatitis B virus, Herpes Virus, Respiratory syncytial virus, Chandipura virus and Influenza A/H1N1. Considering the lack of acceptable drug candidates and the growing antimicrobial resistance to existing drug molecules for many emerging viral diseases, medicinal plants may offer best platform to develop sustainable/efficient/economic alternatives against viral infections. In this regard, for exploring and analyzing large volume of scientific data, bibliometric analysis was done using VOS Viewer shedding light on the emerging areas in the field of medicinal plants and their antiviral activity. This review covers most of the plant species that have some novel bioactive compound like gnidicin, gniditrin, rutin, apigenin, quercetin, kaempferol, curcumin, tannin and oleuropin which showed high efficacy to inhibit the several disease causing virus and their mechanism of action in HIV, Covid-19, HBV and RSV were discussed. Moreover, it also delves the in-depth mechanism of medicinal with challenges and future prospective. Therefore, this work delves the key role of environment in the biological field.

Mechanistic investigation of formation of highly-dispersed silver nanoparticles using sea buckthorn extract.

Nowadays, the greener pathways for the synthesis of nanostructures are being explored. The extracts of different parts of plantsvizleaves, stems, and roots have been investigated. However, these extracts have been prepared by simply boiling or microwaving, or sonicating the parts of plants with water. Therefore, to have deeper insight and to investigate the full potential of plant extracts, serial extraction of leaves of sea buckthorn (Hippophae rhamnoides L.) which is a medicinally important plant was attempted using the soxhlet apparatus. The as-obtained polyphenolic-rich extract was employed for the preparation of silver nanoparticles (Ag-NPs). Under optimized reaction conditionsviz60 °C temperature and 500µl of extract solution (5 mg ml-1) highly disperse spherical nanoparticles of the average size of 15.8 ± 4.8 nm were obtained. Further, the optical band gap of Ag-NPs prepared using optimized reaction conditions was found to be 2.6 eV using the Tauc equation. Additionally, to understand the reduction by the extract, kinetic studies were also carried out which suggest the predominant occurrence of pseudo-first-order reaction. Furthermore, the mechanism of formation of Ag-NPs using major components of extractvizgallic acid and catechin which were identified by HPLC were also investigated using DFT. The mechanistic investigation was performed for both the keto-enol and radical-mediated preparation of Ag-NPs. Such theoretical investigations will help in the efficient designing of greener and novel routes for the synthesis of Ag-NPs. Additionally, the prepared silver was also employed for the colorimetric detection of H2O2.

An Observational Study on the Effect of Yoga and Sudarshan Kriya in Type 2 Diabetes Mellitus Patients.

Introduction One of the major health problems in many countries including India is type 2 diabetes. Yoga is being explored as an alternative therapy for the management of diabetes. Methods Among the total of 137 participants who successfully completed the 'Living Well' workshop by the Art of Living, 84 with type 2 diabetes were assessed for change in random blood sugar levels, systolic and diastolic blood pressure levels (SBP/DBP), and pulse rate over seven days. In the Living Well workshop, the participants performed a comprehensive Yogic Breathing Program that included yogic movements and postures (Asana), relaxation practice, three-stage Pranayama, Sudarshan Kriya Yoga (SKY), breathing techniques, and discussion of stress relieving principles over those seven days. The parameters were recorded at the time of enrollment and after the completion of seven days of the workshop. Results There was a greater (p<0.05) percent reduction in the mean blood sugar level in diabetics as compared to non-diabetic individuals. However, the reduction in SBP and DBP were similar (p>0.05) in diabetics and non-diabetics. The percent reduction in the pulse rate however was greater (p<0.05) in diabetics than non-diabetics. Conclusion Comprehensive yogic breathing practices comprising SKY may be beneficial in patients with type 2 diabetes mellitus.

Assessment of yogic relaxation techniques for its anxiolytic effects in patients requiring endodontic treatment: A prospective, randomized controlled study.

BACKGROUND: The aim of the study is to assess the anxiolytic effects of yogic relaxation technique (YRT) in patients requiring root canal treatment (RCT). MATERIALS AND METHODS: In this prospective, randomized, placebo-controlled study, 30 patients undergoing RCT with baseline visual analog scale for anxiety (VAS-A) of score >4 were divided into Group 1: YRTs; Group 2: alprazolam (0.25 mg/0.5 mg), and Group 3: placebo. After 30 min of completion of YRT, endodontic treatment was performed. Reduction in anxiety was analyzed using state anxiety score (domain) of the state-trait anxiety inventory scale. RESULTS: There was no significant difference in anxiety score 1 h before RCT between groups (P = 0.401). Ten minutes before (P < 0.0001) and after RCT (P < 0.0001), there was significant difference between groups (yogic relaxation vs. alprazolam [P < 0.0001]; yogic relaxation vs. placebo [P < 0.0001]). Ten minutes before RCT, yoga relaxation showed significant difference in anxiety score for pain versus alprazolam and placebo (P < 0.0001 for both). Ten minutes after RCT, the change from baseline in mean anxiety score for pain was significantly different with yogic relaxation (versus alprazolam [P = 0.043]; versus placebo [P = 0.002]). As per the global assessment of efficacy, the response was excellent in 9 (90%), 2 (20%), and 1 (10%) patients in yoga relaxation group, alprazolam group, and placebo group, respectively. Difference in response between three groups was significant (P < 0.0001). There was no significant difference in the global assessment of tolerability between three groups (P = 0.535). No adverse events were reported. CONCLUSION: Before RCT, YRT is an effective alternative to anxiolytic agents, alprazolam.

An acridine derivative, [4,5-bis{(N-carboxy methyl imidazolium)methyl}acridine] dibromide, shows anti-TDP-43 aggregation effect in ALS disease models.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with aggregation of TAR DNA-binding protein-43 (TDP-43) in neuronal cells and manifests as motor neuron dysfunction &muscle atrophy. The carboxyl-terminal prion-like domain of TDP-43 can aggregate in vitro into toxic ß-sheet rich amyloid-like structures. So far, treatment options for ALS are very limited and Riluzole, which targets glutamate receptors, is the only but highly ineffective drug. Therefore, great interest exists in developing molecules for ALS treatment. Here, we have examined certain derivatives of acridine containing same side chains at position 4 &5, for inhibitory potential against TDP-43 aggregation. Among several acridine derivatives examined, AIM4, which contains polar carboxyl groups in the side arms, significantly reduces TDP-43-YFP aggregation in the powerful yeast model cell and also abolishes in vitro amyloid-like aggregation of carboxyl terminal domain of TDP-43, as observed by AFM imaging. Thus, AIM4 can be a lead molecule potentiating further therapeutic research for ALS.

Gedunin and photogedunin of Xylocarpus granatum possess antifilarial activity against human lymphatic filarial parasite Brugia malayi in experimental rodent host.

The present study is aimed to evaluate antifilarial activity of Xylocarpus granatum (fruit from Andaman) against human lymphatic filarial parasite Brugia malayi in vivo. The in vitro antifilarial activity has already been reported earlier for this mangrove plant which has traditionally been used against several ailments. Aqueous ethanolic crude extract, four fractions (ethyl acetate fraction, n-butanol fraction, water-soluble fraction and water-insoluble fraction) and pure molecule/s of X. granatum (fruit) were tested in vitro on adult worms and microfilariae (mf) of B. malayi and the active samples were further evaluated in vivo in B. malayi (intraperitoneally) i.p. transplanted in the jird model (Meriones unguiculatus) and Mastomys coucha subcutaneously infected with infective larvae (L3). The crude aqueous ethanolic extract was active in vitro (IC50: adult = 15.46 µg/ml; mf = 13.17 µg/ml) and demonstrated 52.8% and 62.7% adulticidal and embryostatic effect on B. malayi, respectively, in Mastomys at a dose of 5 × 50 mg/kg by oral route. The antifilarial activity was primarily localized in the ethyl acetate-soluble fraction which revealed IC50 of 8.5 and 6.9 µg/ml in adult and mf, respectively. This fraction possessed moderate adulticidal and embryostatic action in vivo in Mastomys. Out of eight pure molecules isolated from the active fraction, two compounds gedunin (IC50 = 0.239 µg/ml, CC50 = 212.5 µg/ml, SI = 889.1) and photogedunin (IC50 = 0.213 µg/ml, CC50 = 262.3 µg/ml, SI = 1231.4) at 5 × 100 mg/kg by subcutaneous route revealed excellent adulticidal efficacy resulting in to the death of 80% and 70% transplanted adult B. malayi in the peritoneal cavity of jirds respectively in addition to noticeable microfilaricidalo action on the day of autopsy. The findings reveal that the extract from the fruit X. granatum contains promising in vitro and in vivo antifilarial activity against human lymphatic filarial parasite B. malayi which could be attributed to the presence of two pure compounds gedunin and photogedunin.