Exploring the role of natural bioactive molecules in genitourinary cancers: how far has research progressed?

The primary approaches to treat cancerous diseases include drug treatment, surgical procedures, biotherapy, and radiation therapy. Chemotherapy has been the primary treatment for cancer for a long time, but its main drawback is that it kills cancerous cells along with healthy ones, leading to deadly adverse health effects. However, genitourinary cancer has become a concern in recent years as it is more common in middle-aged people. So, researchers are trying to find possible therapeutic options from natural small molecules due to the many drawbacks associated with chemotherapy and other radiation-based therapies. Plenty of research was conducted regarding genitourinary cancer to determine the promising role of natural small molecules. So, this review focused on natural small molecules along with their potential therapeutic targets in the case of genitourinary cancers such as prostate cancer, renal cancer, bladder cancer, testicular cancer, and so on. Also, this review states some ongoing or completed clinical evidence in this regard.

Fluorescent-Nanoparticle-Impregnated Nanocomposite Polymeric Gels for Biosensing and Drug Delivery Applications.

Nanocomposite polymeric gels infused with fluorescent nanoparticles have surfaced as a propitious category of substances for biomedical purposes owing to their exceptional characteristics. The aforementioned materials possess a blend of desirable characteristics, including biocompatibility, biodegradability, drug encapsulation, controlled release capabilities, and optical properties that are conducive to imaging and tracking. This paper presents a comprehensive analysis of the synthesis and characterization of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels, as well as their biomedical applications, such as drug delivery, imaging, and tissue engineering. In this discourse, we deliberate upon the merits and obstacles linked to these substances, encompassing biocompatibility, drug encapsulation, optical characteristics, and scalability. The present study aims to provide an overall evaluation of the potential of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels for biomedical applications. Additionally, emerging trends and future directions for research in this area are highlighted.

The COSPAR Planetary Protection Policy for robotic missions to Mars: A review of current scientific knowledge and future perspectives.

Planetary protection guidance for martian exploration has become a notable point of discussion over the last decade. This is due to increased scientific interest in the habitability of the red planet with updated techniques, missions becoming more attainable by smaller space agencies, and both the private sector and governments engaging in activities to facilitate commercial opportunities and human-crewed missions. The international standards for planetary protection have been developed through consultation with the scientific community and the space agencies by the Committee on Space Research's (COSPAR) Panel on Planetary Protection, which provides guidance for compliance with the Outer Space Treaty of 1967. In 2021, the Panel evaluated recent scientific data and literature regarding the planetary protection requirements for Mars and the implications of this on the guidelines. In this paper, we discuss the COSPAR Planetary Protection Policy for Mars, review the new scientific findings and discuss the next steps required to enable the next generation of robotic missions to Mars.

Effects of combined arsenic and lead exposure on the brain monoaminergic system and behavioral functions in rats: Reversal effect of MiADMSA.

In this study, we evaluated the therapeutic efficacy of monoisoamyldimercaptosuccinic acid (MiADMSA) against individual and combined effects of arsenic (As) and lead (Pb) on the monoaminergic system and behavioral functions in rats. Pregnant rats were exposed to sodium metaarsenite (50 ppm) and lead acetate (0.2%) individually and in combination (As = 25 ppm + Pb = 0.1%) via drinking water from gestation day (GD) 6 to postnatal day (PND) 21. MiADMSA (50 mg/kg body weight) was given orally through gavage for 3 consecutive days to pups from PND 18 to PND 20. The results showed increases in synaptosomal epinephrine, dopamine, and norepinephrine levels with individual metal exposures and decreases with combined exposure to As and Pb in the cortex, cerebellum, and hippocampus in PND 21, PND 28, and 3 months age-group rats. We found decreased activity of mitochondrial monoamine oxidase in the selected brain regions following individual and combined exposures to Pb and As. In addition, rats treated with Pb and As alone or in combination showed significant deficits in open-field behavior, grip strength, locomotor activity, and exploratory behavior at PND 28 and 3 months of age. However, MiADMSA administration showed reversal effects against the As- and/or Pb-induced impairments in the monoaminergic system as well as in behavioral functions of rats. Our data demonstrated that the mixture of Pb and As induced synergistic toxicity to developing brain leading to impairments in neurobehavioral functions and also suggest therapeutic efficacy of MiADMSA against Pb- and/or As-induced developmental neurotoxicity.

Sirtuin 1 and 7 mediate resveratrol-induced recovery from hyper-anxiety in high-fructose-fed prediabetic rats.

Hyperglycaemia in diabetes is either caused by reduced availability of insulin (type 1 diabetes, T1D) or insulin resistance to the cells (type 2 diabetes, T2D). In recent years, the prevalence of T2D has increased to an alarming proportion, encompassing 95 percent of the total diabetic burden, probably due to economy-driven changes in lifestyle. Recent epidemiological studies show comorbid depression, anxiety and related mental illness. To explore the molecular mechanisms underlying this comorbid conditions, we used Sprague-Dawley rats on high-fructose diet for 8 weeks to induce prediabetic condition. Rats with this metabolic syndrome also showed hyper-anxiety when they were subjected to anxiety-related behavioural assays. Rats were administered with resveratrol, an activator of sirtuins, and metformin, a standard antidiabetic drug, simultaneously with fructose. We observed that resveratrol was more effective in protecting from both the metabolic (prediabetic) and affective (anxiety) disorders than metformin. Molecular studies showed that recovery was associated with the upregulation of few nuclear sirtuins that act epigenetically - Sirt 1 and 7, which were significantly attenuated in the striatum of prediabetic rats. In conclusion, our study showed that hyper-anxiety associated with prediabetic condition is ameliorated by resveratrol through modulation of sirtuins, which is more or less similar to metformin.

Pervaporation performance of PPO membranes in dehydration of highly hazardous mmh and udmh liquid propellants.

Polyphenylene oxide (PPO) membranes synthesized from 2,6-dimethyl phenol monomer were subjected to pervaporation-based dehydration of the highly hazardous and hypergolic monomethyl hydrazine (MMH) and unsymmetrical dimethyl hydrazine (UDMH) liquid propellants. Membranes were characterized by TGA, DSC and SEM to study the effect of temperature besides morphologies of surface and cross-section of the films, respectively. Molecular dynamics (MD) simulation was used to study the diffusion behavior of solutions within the membrane. CFD method was employed to solve the governing mass transfer equations by considering the flux coupling. The modeling results were highlighted by the experimental data and were in good agreement. High separation factors (35-70) and reasonable water fluxes (0.1-0.2 kg/m(2)h) were observed for separation of the aqueous azeotropes of MMH (35 wt%) and UDMH (20 wt%) and their further enrichment to >90% purity. Effect of feed composition, membrane thickness and permeate pressure on separation performance of PPO membranes were investigated to determine optimum operating conditions.

Association between neuropeptide Y gene polymorphisms and alcohol dependence: a case-control study in two independent populations.

BACKGROUND: Alcohol dependence is a chronic, progressive neurobiological brain disorder. Previous research reported an inverse association between ethanol drinking and cerebral neuropeptide Y (NPY) levels. There are conflicting results of studies on NPY gene polymorphisms in association with alcohol dependence in humans. METHODS: To assess the role of the NPY gene in alcohol dependence, we genotyped three polymorphisms--in a sample of 195 subjects from the Kota population (80 alcohol dependence and 115 controls) and 141 subjects from the Badaga population (80 alcohol dependence and 61 controls). Phenotype was defined based on the DSM-IV criteria. Genotyping was performed using sequencing. Association of the NPY gene with alcohol dependence was tested by using logistic regression and haplotype analyses and linkage disequilibrium. RESULTS: All three polymorphisms were found to be in the Hardy-Weinberg equilibrium in both populations. The results of our study reveal a significant association between G1258A and alcohol dependence in both the Kota and Badaga populations. The linkage disequilibrium between the markers is not strong or significant. Haplotype analysis also did not show significant association between the NPY gene and alcohol dependence. CONCLUSION: These data support the hypothesis that alcohol dependence is influenced by the NPY G1258A polymorphism in Indian populations.

Genome wide analysis and comparative docking studies of new diaryl furan derivatives against human cyclooxygenase-2, lipoxygenase, thromboxane synthase and prostacyclin synthase enzymes involved in inflammatory pathway.

In an effort to develop potent anti-inflammatory and antithrombotic drugs, a series of new 4-(2-phenyltetrahydrofuran-3-yl) benzene sulfonamide analogs were designed and docked against homology models of human cyclooxygenase-2 (COX-2), lipoxygenase and thromboxane synthase enzymes built using MODELLER 7v7 software and refined by molecular dynamics for 2 ns in a solvated layer. Validation of these homology models by procheck, verify-3D and ERRAT programs revealed that these models are highly reliable. Docking studies of 4-(2-phenyltetrahydrofuran-3-yl) benzene sulfonamide analogs designed by substituting different chemical groups on benzene rings replacing 1H pyrazole in celecoxib with five membered thiophene, furan, 1H pyrrole, 1H imidazole, thiazole and 1,3-oxazole showed that diaryl furan molecules showed good binding affinity towards mouse COX-2. Further, docking studies of diaryl furan derivatives are likely to have superior thromboxane synthase and COX-2 selectivity. Docking studies against site directed mutagenesis of Arg120Ala, Ser530Ala, Ser530Met and Tyr355Phe enzymes displayed the effect of inhibition of COX-2. Drug likeliness and activity decay for these inhibitors showed that these molecules act as best drugs at very low concentrations.

Allelic variation and haplotype structure of the dopamine receptor gene DRD2 in nine Indian populations.

The human dopaminergic system is a significant focal point of study in the fields of neuropsychiatry and pharmacology, plus it is also a promising nuclear DNA marker in studies of human genome diversity. In this study, we assayed six polymorphic markers in the dopamine D2 receptor gene (DRD2) in 482 unrelated individuals from nine ethnic populations of India. Our results demonstrate that the six markers are highly polymorphic in all populations and the constructed haplotypes show a high level of heterozygosity. Out of the eight possible three-site haplotypes, all populations commonly shared only three haplotypes. The haplotypes exhibited fairly high frequencies across multiple populations; Kurumba population showed all eight three-site haplotypes. The ancestral haplotype (B2-D2-Al) was observed at high frequency only in the Siddi population. Haplotypes based on all six markers revealed 16 haplotypes, out of which only 6 are most common with a frequency of greater than 5% in at least one of the nine populations. But only three haplotypes were shared by all nine populations with the cumulative frequency ranging from 80.8% (Kurumba) to 96.6% (Onge). Great variation in levels of linkage disequilibrium (LD) was detected, ranging from complete LD in the Badaga to virtually no LD in the Siddi. This range of LD likely reflects different population histories, such as African ancestry in the Siddi and recent founding events in the population isolates, Badaga and Kota.

Further characterization of Mitsunobu-type intermediates in the reaction of dialkyl azodicarboxylates with P(III) compounds.

Structural characterization of compounds analogous to the proposed intermediates in the Mitsunobu esterification process is achieved by the combined use of NMR spectroscopy and X-ray diffractometric studies. The results show that compounds (t-BuNH)P(mu-N-t-Bu)(2)P[(N-t-Bu)(N-(CO(2)R)-N(H)(CO(2)R))] [R = Et (11), i-Pr (12)], obtained by treating [(t-Bu-NH)P-mu-N-t-Bu](2) (10) with diethylazodicarboxylate (DEAD) or diisopropylazodicarboxylate (DIAD), respectively, have a structure with the NH proton residing between the two nitrogen atoms ((P)N(t-Bu) and (P)N-N(CO(2)Et)); this is the tautomeric form of the expected betaine (t-BuNH)P(mu-N-t-Bu)(2)P(+)[(NH-t-Bu)(N-(CO(2)R)-N(-)(CO(2)R)]. Treatment of ClP(mu-N-t-Bu)(2)P[(N-t-Bu){N-(CO(2)-i-Pr)-N(H)(CO(2)-i-Pr)] (6) with 2,6-dicholorophenol affords (2,6-Cl(2)-C(6)H(3)-O)P(mu-N-t-Bu)(2)P(+)[(NH-t-Bu){N[(CO(2)i-Pr)(HNCO(2)i-Pr)]}](Cl(-))(2,6-Cl(2)-C(6)H(3)-OH) (14) that has a structure similar to that of (CF(3)CH(2)O)P(mu-N-t-Bu)(2)P(+)[(NH-t-Bu){N[(CO(2)i-Pr)(HNCO(2)i-Pr)]}](Cl(-)) (13), but with an additional hydrogen bonded phenol. Both of these have the protonated betaine structure analogous to that of Ph(3)P(+)N(CO(2)R)NH(CO(2)R)(R'CO(2))(-) (2) proposed in the Mitsunobu esterification. Two other compounds, (ArO)P(mu-N-t-Bu)(2)P(+)(NH-t-Bu){N(CO(2)i-Pr)(HNCO(2)i-Pr)}(Cl(-)) [Ar = 2,6-Me(2)C(6)H(3)O- (15) and 2-Me-6-t-Bu-C(6)H(3)-O- (16)], are also prepared by the same route. Although NMR tube reactions of 11 or 12 with tetrachlorocatechol, catechol, 2,2'-biphenol, and phenol revealed significant changes in the (31)P NMR spectra, attempted isolation of these products was not successful. On the basis of (31)P NMR spectra, the phosphonium salt structure (t-BuNH)P(mu-N-t-Bu)(2)P(+)[(HN-t-Bu){N-(CO(2)R)-N(H)(CO(2)R)](ArO(-)) is proposed for these. The weakly acidic propan-2-ol or water did not react with 11 or 12. Treatment of 12 with carboxylic acids/ p-toluenesulfonic acid gave the products (t-BuNH)P(mu-N-t-Bu)(2)P(+)[(HN-t-Bu){N-(CO(2)-i-Pr)-N(H)(CO(2)-i-Pr)](ArCO(2)(-)) [Ar = Ph (18), 4-Cl-C(6)H(4)CH(2) (19), 4-Br-C(6)H(4) (20), 4-NO(2)-C(6)H(4) (21)] and (t-BuNH)P(mu-N-t-Bu)(2)P(+)[(HN-t-Bu){N-(CO(2)-i-Pr)-N(H)(CO(2)-i-Pr)](4-CH(3)-C(6)H(4)SO(3)(-)) (22) that have essentially the same structure as 2. Compound 18 has additional stabilization by hydrogen bonding, as revealed by X-ray structure determination. Finally it is shown that the in situ generated (t-BuNH)P(mu-N-t-Bu)(2)P(+)[(HN-t-Bu){N-(CO(2)Et)-N(H)(CO(2)Et)](4-NO(2)-C(6)H(4)CO(2)(-)) can also effect Mitsunobu esterification. A comparison of the Ph(3)P-DIAD system with the analogous synthetically useful Ph(3)P-dimethyl acetylenedicarboxylate (DMAD) system is made.

A stability indicating LC method for rivastigmine hydrogen tartrate.

An isocratic, reversed-phase liquid chromatographic (RPLC) method was developed for the quantitative determination of Rivastigmine hydrogen tartrate, a cholinesterase inhibitor in bulk drugs and in pharmaceutical dosage forms. The developed method is also applicable for the related substance determination of Rivastigmine hydrogen tartrate in bulk drugs. The chromatographic separation was achieved on a Waters X Terra RP18 (250 mm x 4.6 mm, 5 microm) column using aqueous 0.01 M sodium-1-heptane sulphonate (pH: 3.0 with dilute phosphoric acid)-acetonitrile (72:28, v/v) as a mobile phase. The chromatographic resolution between Rivastigmine and its potential impurity, namely (S)-3-(1-dimethylaminoethyl) phenol (Imp 1) was found to be greater than four. Forced degradation studies were performed for Rivastigmine hydrogen tartrate bulk drug using acid (0.5 N hydrochloric acid), base (0.5 N sodium hydroxide), oxidation (3% hydrogen peroxide), heat (60 degrees C) and UV light (254 nm). No degradation was observed for Rivastigmine hydrogen tartrate except in base hydrolysis and the formed degradation product was found to be Imp 1. The mass balance of Rivastigmine hydrogen tartrate was close to 100 in all the stress conditions. The limit of detection (LOD) and limit of quantification (LOQ) of Imp 1 were found to be 100 and 300 ng/ml, respectively, for 10 microl injection volume. The percentage recovery of Imp 1 in bulk drug sample was ranged from 95.2 to 104.3. The active pharmaceutical ingredient was extracted from its finished dosage form (capsule) using water. The percentage recovery of Rivastigmine hydrogen tartrate was ranged from 99.2 to 101.3 and 98.6 to 101.5 in bulk and pharmaceutical formulation samples, respectively. Rivastigmine hydrogen tartrate sample solution and mobile phase were found to be stable for at least 48 h. The developed method was validated with respect to linearity, accuracy, precision, robustness and forced degradation studies prove the stability indicating power of the method.