Prevalence and impact of pulmonary hypertension on acute decompensated heart failure with preserved ejection fraction hospitalizations: A five-year retrospective analysis.

Heart Failure with Preserved Ejection Fraction (HFpEF) is a major and common cardiovascular condition with widely variable clinical outcomes. Pulmonary hypertension (PH) often co-exists with HFpEF and tends to affect patient outcomes; this study aims to identify the impact of PH on the clinical outcome of patients admitted to the hospital with acute HFpEF exacerbations. We analyzed data from the National Inpatient Sample between 2016 and 2020, focusing on 464,438 acute HFpEF exacerbation hospitalizations. Outcomes were compared between those with PH (27.1 %) and those without PH (72.9 %). HFpEF hospitalizations with PH exhibited elevated in-hospital mortality (adjusted odds ratio [aOR]: 1.20, 95 % confidence interval [95 CI]: 1.08-1.31, P < 0.05), prolonged length of stay (adjusted ß: 0.90 days, P < 0.05), and increased overall costs (adjusted ß: $2,858, P < 0.05). Furthermore, HFpEF hospitalizations with PH demonstrated higher rates of atrial fibrillation, ventricular tachycardia, right ventricular failure, and conduction abnormalities. This population also displayed an increased incidence of acute hypoxic respiratory failure, necessitating increased non-invasive and mechanical ventilation. The co-existence of PH in HFpEF presents an increased risk of mortality and morbidity, with higher healthcare costs and the need for ventilatory support, in addition to higher risks of cardiovascular and pulmonary complications. Therefore, an early diagnosis of PH in patients with HFpEF is crucial, and further research is required to determine appropriate management.

Neighbouring effect of land use changes and fire emissions on atmospheric CO2 and CH4 over suburban region of India (Shadnagar).

The present study investigated the effects of land use/land cover (LU/LC) changes on atmospheric carbon dioxide (CO2) and methane (CH4) concentrations over the sub-urban region of India (Shadnagar) using continuous decadal CO2 and CH4in-situ data measured by the greenhouse gas analyser (GGA). Data was collected from 2013 to 2022 at a 1 Hz frequency. Analysis of the current study indicates that during pre-monsoon, the seasonal maximum of CO2 was 409.91 ± 9.26 ppm (µ ± 1σ), while the minimum during monsoon was about 401.64 ± 7.13 ppm. Post-monsoon has a high seasonal mean CH4 concentration of 2.08 ± 0.06 ppm, while monsoon has a low seasonal mean CH4 concentration of 1.88 ± 0.03 ppm. The primary classes, such as forest, crop, and built-up, were considered to estimate the effect of LU/LC changes on atmospheric CO2 and CH4 concentrations. Between 2005 and 2021, the study's results show that the built-up area at radii of 10 km, 20 km, and 50 km increased by 0.17 %, 0.10 %, and 0.4 %, respectively. While other LU/LC categories declined by 30 %, agriculture areas increased by 30 % on average. As a result, the CO2 and CH4 concentrations at the study site are increased by 6 % (26 ppm) and 6.5 % (140 ppb), respectively. The present study utilised the fire-based carbon emissions data from the Global Fire Emissions Database (GFED) to understand the impact on atmospheric CO2 and CH4. Analysis of the present work investigated the influence of transported airmass on CO2 and CH4 during the pre-monsoon and post-monsoon seasons using the HYSPLIT trajectories and found emissions were from the northwest, southeast, and northeast of the study site. Further, in-situ CO2 and CH4 records are compared against the MIROC4-ACTM simulation, and strong agreement was found with bias of 1.80 ppm and 0.98 ppb for CO2 and CH4, respectively.

Montmorillonite K10 Clay Catalyzed Synthesis of Novel ß-Aminocarbonyl Compounds and Their Biological Evaluation.

An efficient and reusable green catalyst for the synthesis of ß-aminocarbonyl compounds has been developed. In this new and greener approach, ß-aminocarbonyl compounds (1a-1r) were obtained by Montmorillonite K10 clay catalyzed reaction of aryl amines, aliphatic/aromatic aldehydes and ß-ketoesters. Molecular docking investigations were performed for all compounds (1a-1r) with the proteins PDB ID: 1JIJ and 1KZN for S. aureus and E. coli, respectively. For all compounds good to strong interactions with the active sites were observed. The biological activities of ß-aminocarbonyl compounds were further assessed for their antibacterial and antioxidant activities. The results confirmed that ß-aminocarbonyl compounds could be further developed into new drugs with potent antibacterial and antioxidant activities.

Vegetation health conditions assessment and mapping using AVIRIS-NG hyperspectral and field spectroscopy data for -environmental impact assessment in coal mining sites.

This paper focuses on vegetation health conditions (VHC) assessment and mapping using high resolution airborne hyperspectral AVIRIS-NG imagery and validated with field spectroscopy-based vegetation spectral data. It also quantified the effect of mining on vegetation health for geo-environmental impact assessment at a fine level scale. In this study, we have developed and modified vegetation indices (VIs) based model for VHC assessment and mapping in coal mining sites. We have used thirty narrow banded VIs based on the statistical measurement for suitable VIs identification. The highest Pearson's r, R2, lowest RMSE, and P values indices have been used for VIs combined pixels analysis. The highest different (Healthy vs. unhealthy) vegetation combination index (VCI) has been selected for VHC assessment and mapping. We have also compared VIs model-based VHC results to ENVI (software) forest health tool and Spectral-based SAM classification results. The 1st VCI result showed the highest difference (72.07%) from other VCI. The AUC values of the ROC curve have shown a better fit for the VIs model (0.79) than Spectral classification (0.74), and ENVI FHT (0.68) based on VHC results. The VHC results showed that unhealthy vegetation classes are located at low distances from mine sites, and healthy vegetation classes are situated at high distances. It is also seen that there is a highly significant positive relationship (R2 =0.70) between VHC classes and distance from mines. These results will provide a guideline for geo-environmental impact assessment in coal mining sites.

Deforestation susceptibility assessment and prediction in hilltop mining-affected forest region.

This work mainly focused on deforestation susceptibility (DS) assessment and its prediction based on statistical models (FR, LR & AHP) in the Saranda forest, India. Also, efforts had been made to quantify the effect of mining on deforestation. We had considered twenty-five (twenty present and five predicted) causative variables of deforestation, including climate, natural or geomorphological, forestry, topographical, environmental, and anthropogenic. The predicted variables have been generated from different simulation models. Also, very high-resolution, Google Earth imagery have been used in time series analysis for deforestation from 1987 to 2020 data and generated dependent variable. On deforestation analysis, it was observed that a total of 4197.84 ha forest areas were lost in the study region due to illegal mining, agricultural and tribal people allied activities. The DS results have shown that of total existing forest area, 11.22% area were under very high, 16.08% under high, 16.18% under moderate, 24.25% under low, and 32.27% falls very low categories. According to the DS assessment and predicted results, the very high susceptibility classes were found at and close to mines, agricultural, roads and settlement's surrounding sites. The sensitivity analysis results also shown that some causative variables (maximum temperature (2.95%), minimum temperature (0.51%), rainfall (2.69%), LST (4.56%), hot spot (7.36%), aspect (1.14%), NDVI (2.64%), forest density (3.78%), lithology (3.26%), geomorphology (3.00%), distance from agricultural (19.40%), soil type (2.05%), solar radiation (5.97%), LULC (3.26%), drought (3.16%), altitude (2.85%), slope (5.97%), distance from mines (18.05%), roads (2.17%), and settlements (5.18%)) were more sensitive to deforestation. Most of the sensitive parameters showed a positive correlation with DS. The AUC values of the ROC curve had shown a better fit for AHP (0.72) than (0.69) FR and LR (0.68) models for present DS results. The correlation results had shown a good inverse relationship between DS and distance from mines and foliar dust concentration. This work will espouse the future work in the effective planning and management of the mining-affected forest region and predicted deforestation susceptibility would be helpful for forest ecosystem study and policymaking.

Lycopene Prevents Mitochondrial Dysfunction during d-Galactosamine/Lipopolysaccharide-Induced Fulminant Hepatic Failure in Albino Rats.

Functional perturbation of mitochondria is associated with fulminant hepatic failure (FHF). d-Galactosamine/lipopolysaccharide (d-GalN/LPS)-induced FHF is a renowned model to evaluate the efficacy of hepatoprotective agents. Lycopene is an antioxidant and phytonutrient from the carotenoid family. The health benefits of lycopene are prominent against cancer and cardiovascular, lung, liver, and skin problems. Recent studies have demonstrated the hepatoprotective, antidyslipidemic, and antioxidant roles of lycopene. The current study was designed to appraise the ability of lycopene to prevent mitochondrial dysfunction during the d-GalN/LPS-induced FHF. The administration of d-GalN/LPS (300 mg and 30 µg/kg body weight, respectively) to the experimental rats induced several disturbances in mitochondrial function. The lipid peroxide and hydrogen peroxide levels were increased (p < 0.05). The activities of mitochondrial antioxidants, tricarboxylic acid (TCA) cycle, and electron transport chain enzymes and the cellular adenosine triphosphate (ATP) content were decreased (p < 0.05). Lycopene (10 mg/kg body weight for 6 days) pretreatment attenuated lipid peroxidation and prohibited the excessive synthesis of hydrogen peroxide. The d-GalN/LPS-induced impairment in ATP production and increased enzyme activities were effectively prevented by the lycopene administration. The lycopene-mediated mitochondrial protection was mainly ascribed to the strong antioxidant potential of this phytonutrient. Molecular modeling results obtained show evidence that lycopene inhibits several lipoxygenases and provides rationale for the observed prevention of lipid peroxidation in the mitochondrial membrane. The carotenoid lycopene combatted oxidative stress, scavenged free radicals, prevented ROS generation, and inhibited the toxic effects of d-GalN/LPS during FHF.

Cytotoxicity and cytochrome P450 inhibitory activities of Clinacanthus nutans.

BACKGROUND: Clinacanthus nutans Lindau (family: Acanthaceae), also known as "Sabah Snake Grass" or "Belalai Gajah" in Malaysia, has been widely used by Malaysians due to its anticancer property. However, the anticancer activity of C. nutans leaves extract and its safe use need to be further investigated. The objectives of the present study were to evaluate the cytotoxic effects of methanol leaves extract of C. nutans in various human cancer cell lines and to evaluate the in vitro effect of C. nutans leaves on the activity of CYP3A4 and CYP2E1 in human liver microsomes. METHODS: The cytotoxic effects of methanol extract of C. nutans leaves in various cancer cell lines (Hep-G2, A549, HT-29, MDA-MB-231, MCF-7, and CRL 1739) and normal cells (3T3) were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The activities of CYP3A4 and CYP2E1 were determined using simple spectrophotometric methods. RESULTS: Results obtained showed that the methanol extract of C. nutans leaves exhibited the highest cytotoxic effect against Hep-G2 cell lines (liver cancer) (IC50=13.33 µg/mL), followed by breast cancer oestrogen negative (MDA-MB-231) (IC50 of 18.67 µg/mL). Methanol leaves extract of C. nutans showed significant inhibition (p<0.05) in CYP3A4 and CYP2E1 activity in human liver microsomes. CONCLUSIONS: In conclusion, methanol leaves extract of C. nutans exhibited the highest cytotoxic activity against liver cancer cells (Hep-G2). There is a possibility that herb-drug interaction could occur with C. nutans through inhibitory effects on CYP3A4. Additionally, inhibition of C. nutans on CYP2E1 could show anti-carcinogenesis effects in human liver microsomes.

Anti-hyperalgesic effect of a benzilidine-cyclohexanone analogue on a mouse model of chronic constriction injury-induced neuropathic pain: Participation of the κ-opioid receptor and KATP.

The present study investigated the analgesic effect of a novel synthetic cyclohexanone derivative, 2,6-bis-4-(hydroxyl-3-methoxybenzilidine)-cyclohexanone or BHMC in a mouse model of chronic constriction injury-induced neuropathic pain. It was demonstrated that intraperitoneal administration of BHMC (0.03, 0.1, 0.3 and 1.0mg/kg) exhibited dose-dependent inhibition of chronic constriction injury-induced neuropathic pain in mice, when evaluated using Randall-Selitto mechanical analgesiometer. It was also demonstrated that pretreatment of naloxone (non-selective opioid receptor blocker), nor-binaltorphimine (nor-BNI, selective κ-opioid receptor blocker), but not ß-funaltrexamine (ß-FN, selective µ-opioid receptor blocker) and naltrindole hydrochloride (NTI, selective δ-opioid receptor blocker), reversed the anti-nociceptive effect of BHMC. In addition, the analgesic effect of BHMC was also reverted by pretreatment of 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ, soluble guanosyl cyclase blocker) and glibenclamide (ATP-sensitive potassium channel blocker) but not Nω-nitro-l-arginine (l-NAME, a nitric oxide synthase blocker). Taken together, the present study demonstrated that the systemic administration of BHMC attenuated chronic constriction, injury-induced neuropathic pain. We also suggested that the possible mechanisms include κ-opioid receptor activation and nitric oxide-independent cyclic guanosine monophosphate activation of ATP-sensitive potassium channel opening.

New flavan and alkyl alpha,beta-lactones from the stem bark of Horsfieldia superba.

In the present study phytochemical investigation of the methanol extract of the stem bark of Horsfieldia superba led to the isolation of twenty compounds (1-20), of which three (1-3) were new. However, compounds 2 and 3 were previously reported as synthetic alpha,beta-lactones. The compounds were characterized as (-)-3,4',7-trihydroxy-3'-methoxyflavan (1), (-)-5,6-dihydro-6-undecyl-2H-pyran-2-one (2), and (-)-5,6-dihydro-6-tridecyl-2H-pyran-2-one (3). Seventeen other known compounds were also isolated and identified as (-)-viridiflorol (4), hexacosanoic acid (5), beta-sitosterol (6), methyl 2,4-dihydroxy-6-methylbenzoate (methylorsellinate) (7), methyl 2,4-dihydroxy-3,6-dimethylbenzoate (8), (-)-4'-hydroxy-7-methoxyflavan (9), (-)-4',7-dihydroxyflavan (10), (-)-4',7-dihydroxy-3'-methoxyflavan (11), (+)-3,4',7-trihydroxyflavan (12), (-)-catechin (13), (-)-epicatechin (14), (-)-7-hydroxy-3',4'-methylenedioxyflavan (15), 2',3,4-trihydroxy-4'-methoxydihydrochalcone (16), 3',4',7-trihydroxyflavone (17), (+)-4'-hydroxy-7-methoxyflavanone (18), hexadecanoic acid (palmitic acid) (19) and 3,4-dihydroxybenzoic acid (20). The structures of the compounds were fully characterized by various physical methods (melting point, optical rotation), spectral (UV, IR, ID and 2D NMR) and mass spectrometric techniques. In vitro assay of compounds 2 and 3 demonstrated moderate cytotoxic activities against human prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cells, while the chloroform and ethyl acetate fractions of H. superba were found to exhibit moderate AChE inhibitory activity (IC50 72 and 60 microg/mL).

Synthesis of bisindolylmethanes and their cytotoxicity properties.

Polymer supported dichlorophosphate (PEG-OPOCl(2)) is an efficient green catalyst for the electrophilic substitution reaction of indole with aromatic aldehydes, in neat condition, to afford an excellent yield of bis(indolyl) methanes with short reaction time, at room temperature. The synthesized compounds and their anti-cancer activity are evaluated.

Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone, on nociception-induced models in mice.

This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID(50) of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID(50) of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID(50) of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.

Possible participation of nitric oxide/cyclic guanosine monophosphate/protein kinase C/ATP-sensitive K(+) channels pathway in the systemic antinociception of flavokawin B.

The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg/kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with L-arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K(+) channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO/cyclic guanosine monophosphate/PKC/ATP-sensitive K(+) channel pathway possibly participated in the antinociceptive action induced by FKB.

A new di-O-prenylated isoflavone from Tephrosia tinctoria.

A new di-O-prenylated isoflavone, 5,7-di-O-prenylbiochanin A (1), together with three known compounds, 7-O-methylglabranin (2), tephrowatsin C (3) and flemichapparin B (4), were isolated from the stems of Tephrosia tinctoria. The structures of these compounds were elucidated by extensive 2D NMR spectral studies.