Advanced photocatalysis as a viable and sustainable wastewater treatment process: A comprehensive review.

In our era, water pollution not only poses a serious threat to human, animal, and biotic life but also causes serious damage to infrastructure and the ecosystem. A set of physical, chemical, and biological technologies have been exploited to decontaminate and/or disinfect water pollutants, toxins, microbes, and contaminants, but none of these could be ranked as sustainable and scalable wastewater technology. The photocatalytic process can harmonize the sunlight to degrade certain toxins, chemicals, microbes, and antibiotics, present in water. For example, transition metal oxides (ZnO, SnO2, TiO2, etc.), when integrated into an organic framework of graphene or nitrides, can bring about more than 90% removal of dyes, microbial load, pesticides, and antibiotics. Similarly, a modified network of graphitic carbon nitride can completely decontaminate petrochemicals. The present review will primarily highlight the mechanistic aspects for the removal and/or degradation of highly concerned contaminants, factors affecting photocatalysis, engineering designs of photoreactors, and pros and cons of various wastewater treatment technologies already in practice. The photocatalytic reactor can be a more viable and sustainable wastewater treatment opportunity. We hope the researcher will find a handful of information regarding the advanced oxidation process accomplished via photocatalysis and the benefits associated with the photocatalytic-type degradation of water pollutants and contaminants.

Satisfaction of patients in government medical teaching institutes of Peshawar Khyber Pakhtunkhwa, Pakistan: a cross-sectional analytical study.

Objective: To evaluate patient satisfaction and its associated factors in teaching hospitals. METHODS: The cross-sectional, analytical study was conducted from September to December 2022 at three publicsector medical teaching hospitals in Peshawar, Pakistan, and comprised adult patients of either admitted to various hospital wards for at least 2 days. Data was collected using a predesigned a closed-ended questionnaire assessing patient satisfaction in different domains like, facilitation at the admission, professional knowledge and skills of the attending doctors, quality of diagnostic and nursing services, and basic amenities. Data was analysed using SPSS version origin Pro 2022a. RESULTS: There were 473 patients with a male-female ratio of 3:1, with mean age 43.3+14.7 years (range: 11-85 years), and mean hospital stay 5.96+3.37 days (range: 2-18 days). Of the 2,365 response statements for facilitation at the admission counter, 2,051(87%) were positive; of the 2,365 statements for attending doctors, 2,012(85%) were positive; of the 2,838 statements for nursing care, 2,122(75%) were positive; of 946 statements for diagnostic services, 627(66%) were positive; and of the 3,311 statements for basic amenities at the hospital, 1,246(38%) were positive. Overall, of the 11,825 response statements, 8058(68%) were positive. The patient satisfaction was significantly co-related with education and hospital stay (p<0.05). Conclusion: Patients were found to be generally satisfied with healthcare services, but not with the provision of basic amenities.

Milk microbiota of Holstein Friesian cattle reared in Lahore: Association with mastitis.

The dairy industry is reshaping itself and becoming commercialized in Pakistan due to the increased demand for milk to overcome the shortage. Exotic breeds such as Holstein Friesian, a high milk producing breed have started being reared more on farms in Pakistan. Along with other issues, mastitis does affects the milk production of this breed. The objective of this study was to evaluate the milk composition in terms of bacterial communities in Holstein Friesian reared in Punjab, Pakistan and alteration in microbial composition with healthy and mastitic udder. Milk samples (n = 36) from farms rearing Holstein Friesian were collected. Among these samples, 05 samples from each three groups, HHF(healthy), CHF (clinical mastitis) and SHF (subclinical mastitis), based on their udder health condition, were processed using the 16 S r=RNA gene based technique. Diversity assessment as carried out by alpha diversity indices showed that milk samples from the udder infected with clinical mastitis were the least diverse and those from the healthy udder were more diverse. Beta diversity across samples showed a scattered pattern suggesting overlap amongst bacterial communities across different groups samples as depicted by PCA plots of beta diversity indices. The taxonomic profile revealed that Proteobacteria Firmicutes, Bacteroidota and Actinobacteriota were the major phyla detected across all groups. Proteobacteria dominated the HHF and SHF group while abundance of Firmicutes was higher in CHF group. Differences at other levels including order, genus and species were also recorded. The overall picture concludes that diverse microbiota is associated with different udder health conditions.

Successful treatment with fludarabine and cyclophosphamide in a VEXAS syndrome patient with associated myelodysplastic syndrome: a case report and systematic review.

Vacuoles, E1 syndrome, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a chronic inflammatory disorder that affects various organ systems. It is associated with hematologic malignancies and is generally refractory to therapies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for selected patients. We report a case wherein systemic and hematological manifestations completely resolved in a patient with VEXAS and associated myelodysplastic syndrome (MDS), following the administration of fludarabine and cyclophosphamide as part of the preparation for allo-HSCT. We conducted a systematic literature review and included 86 patients with VEXAS syndrome and associated MDS. Most cases presented with musculoskeletal involvement (71%) and anemia (72%) with lower-risk MDS. Most patients responded to corticosteroids (CS) but had a recurrence of symptoms with CS taper and were refractory to other immunosuppressive agents. Hypomethylating agents and Janus kinase inhibitors achieved a complete response in some cases. Further research is needed to develop more effective treatment strategies.

Use of Endpoints in Phase III Randomized Controlled Trials for Hematopoietic Stem Cell Transplantation Over the Last 15 Years: A Systematic Review.

This systematic review aimed to evaluate the proportion of primary and secondary endpoints in hematopoietic stem cell transplant (HSCT) phase III randomized clinical trials (RCTs) and analyze their trends in time and study sponsorship status. The Chi-square test and logistic regression analyses were performed using SPSS version 28. A total of 147 HSCT phase III RCTs from 2006 to 2021 reported 197 primary and 600 secondary endpoints. Overall survival (OS, 17 %), progression-free survival (PFS, 15 %), graft versus host disease (GVHD, 8 %), event-free survival (EFS, 8 %), and organ function (8 %) were the most common primary endpoints. GVHD (12.3 %, n = 74), safety/toxicity/adverse events (11.8 %, n = 71), OS (11.5 %, n = 69), PFS (9.3 %, n = 56), and relapse rate (RR; 7.5 %, n = 45) were the most common secondary endpoints during 2006-2021. After 2013, an increase was noted in the use of PFS as a primary endpoint (12 %-18 %, p = 0.196), while the use of OS as a primary endpoint declined (20 %-13 %, p = 0.170). An increase was observed in using the secondary endpoints RR (5 %-10 %, p = 0.047) and NRM (3 %-6 %, p = 0.047). EFS was used more (14 % vs. 4 %, p = 0.012) than ORR (11 % vs. 2 %, p = 0.003) as a primary endpoint in pharmaceutical-compared to non-pharmaceutical-sponsored studies. As secondary endpoints, the use of EFS (4 % vs. 1 %, p = 0.013) and ORR (4 % vs. 1 %, p = 0.028) was higher, whereas that of organ systems/functions (1.5 % vs. 5.5 %, p = 0.022) and GVHD (6.5 % vs. 15 %, p = 0.002) was lower in pharmaceutical-compared to non-pharmaceutical sponsored studies. GVHD-free relapse-free survival was reported as a primary endpoint in 2 % of studies, while only 5 % reported quality of life as a secondary endpoint. We described commonly used endpoints in HSCT phase III RCTs and patterns in their use over time by funding source and study intervention category.

Endogenous Interfacial Mo-C/N-Mo-S Bonding Regulates the Active Mo Sites for Maximized Li+ Storage Areal Capacity.

Active sites, mass loading, and Li-ion diffusion coefficient are the benchmarks for boosting the areal capacity and storage capability of electrode materials for lithium-ion batteries. However, simultaneously modulating these criteria to achieve high areal capacity in LIBs remains challenging. Herein, MoS2 is considered as a suitable electroactive host material for reversible Li-ion storage and establish an endogenous multi-heterojunction strategy with interfacial Mo-C/N-Mo-S coordination bonding that enables the concurrent regulation of these benchmarks. This strategy involves architecting 3D integrated conductive nanostructured frameworks composed of Mo2 C-MoN@MoS2 on carbon cloth (denoted as C/MMMS) and refining the sluggish kinetics in the MoS2 -based anodes. Benefiting from the rich hetero-interface active sites, optimized Li adsorption energy, and low diffusion barrier, C/MMMS reaches a mass loading of 12.11 mg cm-2 and showcases high areal capacity and remarkable rate capability of 9.6 mAh cm-2 @0.4 mA cm-2 and 2.7 mAh cm-2 @6.0 mA cm-2 , respectively, alongside excellent stability after 500 electrochemical cycles. Moreover, this work not only affirms the outstanding performance of the optimized C/MMMS as an anode material for supercapacitors, underscoring its bifunctionality but also offers valuable insight into developing endogenous transition metal compound electrodes with high mass loading for the next-generation high areal capacity energy storage devices.

Multivalent Sulfur Vacancy-Rich NiCo2 S4 @MnO2 Urchin-Like Heterostructures for Ambient Electrochemical N2 Reduction to NH3.

Innovative advances in the exploitation of effective electrocatalytic materials for the reduction of nitrogen (N2 ) to ammonia (NH3 ) are highly required for the sustainable production of fertilizers and zero-carbon emission fuel. In order to achieve zero-carbon footprints and renewable NH3 production, electrochemical N2 reduction reaction (NRR) provides a favorable energy-saving alternative but it requires more active, efficient, and selective catalysts. In current work, sulfur vacancy (Sv)-rich NiCo2 S4 @MnO2 heterostructures are efficaciously fabricated via a facile hydrothermal approach followed by heat treatment. The urchin-like Sv-NiCo2 S4 @MnO2 heterostructures serve as cathodes, which demonstrate an optimal NH3 yield of 57.31 µg h-1  mgcat -1 and Faradaic efficiency of 20.55% at -0.2 V versus reversible hydrogen electrode (RHE) in basic electrolyte owing to the synergistic interactions between Sv-NiCo2 S4 and MnO2 . Density functional theory (DFT) simulation further verifies that Co-sites of urchin-like Sv-NiCo2 S4 @MnO2 heterostructures are beneficial to lowering the energy threshold for N2 adsorption and successive protonation. Distinctive micro/nano-architectures exhibit high NRR electrocatalytic activities that might motivate researchers to explore and concentrate on the development of heterostructures for ambient electrocatalytic NH3 generation.

Uniting Synergistic Effect of Single-Ni Site and Electric Field of B- Bridged-N for Boosted Electrocatalytic Nitrate Reduction to Ammonia.

Electrochemical conversion of nitrate, a prevalent water pollutant, to ammonia (NH3 ) is a delocalized and green path for NH3 production. Despite the existence of different nitrate reduction pathways, selectively directing the reaction pathway on the road to NH3 is now hindered by the absence of efficient catalysts. Single-atom catalysts (SACs) are extensively investigated in a wide range of catalytic processes. However, their application in electrocatalytic nitrate reduction reaction (NO3 - RR) to NH3 is infrequent, mostly due to their pronounced inclination toward hydrogen evolution reaction (HER). Here, Ni single atoms on the electrochemically active carrier boron, nitrogen doped-graphene (BNG) matrix to modulate the atomic coordination structure through a boron-spanning strategy to enhance the performance of NO3 - RR is designed. Density functional theory (DFT) study proposes that BNG supports with ionic characteristics, offer a surplus electric field effect as compared to N-doped graphene, which can ease the nitrate adsorption. Consistent with the theoretical studies, the as-obtained NiSA@BNG shows higher catalytic activity with a maximal NH3 yield rate of 168 µg h-1  cm-2 along with Faradaic efficiency of 95% and promising electrochemical stability. This study reveals novel ways to rationally fabricate SACs' atomic coordination structure with tunable electronic properties to enhance electrocatalytic performance.

Predictors of cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation: Insights from a real-world experience.

BACKGROUND: We aimed to investigate factors associated with cytomegalovirus (CMV) viremia and CMV disease and its impact on post-transplant outcomes including overall survival (OS) following allogeneic hematopoietic stem cell transplantation (Allo-SCT). METHODS: We conducted a single-center retrospective study including 452 Allo-SCT recipients (matched unrelated donor, MUD 61%; haploidentical, haplo 39%) from 2016 to 2021. Data were analyzed using SPSS v28. Descriptive (chi-square and t-test), Kaplan-Meier and regression analyses were conducted. RESULTS: The median age was 57 years. Sixty-one percent were males and 84.3% were Caucasians. CMV serostatus was positive in 59.1% of recipients. The median follow-up was 24.4 months. CMV viremia and CMV disease were observed in 181 (40%) and 32 (7%) patients, respectively. Among CMV seropositive recipients, 65% developed CMV viremia and 11% were noted to have CMV disease compared to 4% and 1% in seronegative recipients, respectively (p < 0.001). Patients with CMV disease had significantly lower OS than those without CMV disease (median 14.1 months vs. not reached, p = 0.024); however, OS was not associated with CMV viremia (median not reached in both groups, p = 0.640). Letermovir prophylaxis was used in 66% (n = 176/267) of CMV seropositive recipients, but no impact was observed on the incidence of CMV viremia or CMV disease and OS. CONCLUSIONS: CMV disease leads to significantly inferior survival after an allogeneic hematopoietic cell transplantation. Recipient CMV seropositive status was associated with the risk of CMV viremia and CMV disease, and this was not abrogated with the use of Letermovir prophylaxis.

Outcomes with allogeneic hematopoietic stem cell transplantation in TP53-mutated myelodysplastic syndrome: A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov. After screening 626 articles, eight studies were included. Data were extracted following the PRISMA guidelines and analyzed using the meta-package by Schwarzer et al. We analyzed 540 patients. The pooled median 3 (1-5) year overall survival was 21% (95% CI 0.08-0.37, I2=91%, n=540). The pooled relapse rate was 58.9% (95% CI 0.38-0.77, I2=93%, n=487) at a median of 1.75 (1-3) years. The pooled 4-year progression- free survival was 34.8% (95% CI 0.15-0.57, I2=72%, n=105). Outcomes of Allo-HSCT for TP53-mutated MDS patients remain poor, with 21% OS at three years; however, Allo-HSCT confers a survival advantage as compared to non-transplant palliative therapies. Our findings suggest the need to explore novel therapeutic agents in prospective clinical trials.

A Metal Coordination Number Determined Catalytic Performance in Manganese Borides for Ambient Electrolysis of Nitrogen to Ammonia.

A new strategy that can effectively increase the nitrogen reduction reaction performance of catalysts is proposed and verified by tuning the coordination number of metal atoms. It is found that the intrinsic activity of Mn atoms in the manganese borides (MnBx ) increases in tandem with their coordination number with B atoms. Electron-deficient boron atoms are capable of accepting electrons from Mn atoms, which enhances the adsorption of N2 on the Mn catalytic sites (*) and the hydrogenation of N2 to form *NNH intermediates. Furthermore, the increase in coordination number reduces the charge density of Mn atoms at the Fermi level, which facilitates the desorption of ammonia from the catalyst surface. Notably, the MnB4 compound with a Mn coordination number of up to 12 exhibits a high ammonia yield rate (74.9 ± 2.1 µg h-1 mgcat -1 ) and Faradaic efficiency (38.5 ± 2.7%) at -0.3 V versus reversible hydrogen electrode (RHE) in a 0.1 m Li2 SO4 electrolyte, exceeding those reported for other boron-related catalysts.

Different levels of single-strain probiotic (Bacillus subtilis) with proteolytic enzyme (serratiopeptidase) can be used as an alternative to antibiotic growth promoters in broiler.

In the current study, the proteolytic enzyme (serratiopeptidase) was used to enhance the efficacy of Bacillus subtilis (B. subtilis) probiotic as a growth promotor in broiler chicken. The effects of serratiopeptidase on the efficacy of different levels of B. subtilis as a growth promotor in broiler chicks were evaluated regarding growth performance traits, villus histomorphometric characterization, and intestinal microbiota count. Day-old broiler chicks (n = 120) were allocated into 4 groups having 3 replicates/group. In the control group (C), the basal diet was kept without supplementation. In treatment groups (P100, P150, and P200), the basal diet was supplemented with 100, 150, and 200 mg probiotics, respectively besides 30 mg proteolytic enzyme in the 3 treated groups for 4 wk. The performance parameters were significantly affected by the supplementation of serratiopeptidase to the B. subtilis treatment groups. Feed intake (FI), body weight gain (WG), feed conversion ratio (FCR), and dressing percent were significantly improved in the treatment groups as compared to the control group. Significantly, the lowest feed intake was recorded for the P200 group. The highest body weight gain and dressing percentage were recorded for the P200 group. An improved FCR was recorded in the P200 group (1.7) as compared to the control group. The different levels of B. subtilis supplemented with serratiopeptidase revealed significant improvements (P<0.05) in the morphology of the intestine by showing increases in villus height and width and crypt depth of the small intestine. The microbial count revealed that E. coli and salmonella colonies were significantly reduced in the P200 group as compared to the control and other treatment groups. In conclusion, the supplementation of B. subtilis with serratiopeptidase as a growth promoter in broiler chicks significantly improved the overall performance, and intestinal health and reduced microbial load contributing to optimizing the performance of broiler chickens. The greatest improvement was observed in the P200 group fed with B. subtilis as a probiotic and serratiopeptidase enzyme (200 mg:30 mg).

Historical and current distribution ranges of the Asiatic black bear (Ursus thibetanus).

The current distribution of Asiatic black bear (Ursus thibetanus) is available on the IUCN Red List of Threatened species website; however, nothing is known about the historical extent and occurrence of this species. Therefore, we aimed to understand the historical distribution of the Asiatic black bear, and map and estimate its total size, to compare it with that of species current distribution. In addition, we analyzed a network of protected areas in the past and current ranges of the species. We employed geographic information system (GIS) software to reconstruct and measure the historical range of the Asiatic black bear, comparing past and current ranges to analyze its expected range contraction. The main focus of the study was to enhance our understanding of the species' historical distribution, contributing to better conservation strategies for the present and future perspectives. The utilization of GIS tools facilitates a comprehensive exploration of the factors influencing the species' decline, ultimately aiding in more effective management and conservation efforts. We used published records of black bear's occurrence in anywhere in history to reconstruct its historical distribution range. Results revealed that the Asiatic black bear was more widely distributed in historical times and its range spanned across approximately 15.86 million km2 while its current range is limited to approximately 7.85 million km2, showing a range contraction of approximately 49.5% (8.02 million km2 reduced). The total protected areas in the historical range of the species were found to be N = 9933, with total size of 0.946 million km2, against N = 6580 (0.667 million km2) that are present in the current range. Approximately 27.5% of the protected areas have lost the Asiatic black bear since historical times.

Outcomes with HLA-matched unrelated donor versus haploidentical hematopoietic cell transplantation.

We investigated the outcomes after adult haploidentical (haplo) and matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) in a single-center study (n = 452) including 276 MUD and 176 haplo transplants. Myeloablative (37%) and reduced-intensity conditioning (63%) were performed. Graft sources included peripheral blood (50%) and bone marrow (50%). GVHD prophylaxis included tacrolimus/methotrexate (53%) and post-transplant cyclophosphamide-based (47%). In MUD versus haplo HCT recipients, a similar incidence of neutrophil engraftment (18 vs 17 days, p = 0.895), grade II-IV acute GVHD (51% vs 50%, p = 0.773), relapse (26% vs 23%, p = 0.578), non-relapse mortality (22% vs 23%, p = 0.817), 1-year disease-free survival (62% vs 63%. p = 0.921), and 1-year overall survival (73% vs 74%, p = 0.744) were observed. Earlier platelet engraftment (22 vs 27 days, p < 0.001) and higher chronic GVHD (45% vs 35%, p = 0.040) were noted in MUD as compared to haplo HCT. Allogeneic transplantation should be done promptly whenever indicated, utilizing either matched unrelated or haploidentical donors.

Monolithic Microparticles Facilitated Flower-Like TiO2 Nanowires for High Areal Capacity Flexible Li-Ion Batteries.

Flexible lithium-ion batteries (FLIBs) are intensively studied using free-standing transition metal oxides (TMOs)-based anode materials. However, achieving high areal capacity TMO-based anode materials is yet to be effectively elucidated owing to the poor adhesion of the active materials to the flexible substrate resulting in low active mass loading, and hence low areal capacity is realized. Herein, a novel monolithic rutile TiO2 microparticles on carbon cloth (ATO/CC) that facilitate the flower-like arrangement of TiO2 nanowires (denoted ATO/CC/OTO) is demonstrated as high areal capacity anode for FLIBs. The optimized ATO/CC/OTO anode exhibits high areal capacity (5.02 mAh cm-2 @0.4 mA cm-2 ) excellent rate capability (1.17 mAh cm-2 @5.0 mA cm-2 ) and remarkable cyclic stability (over 500 cycles). A series of morphological, kinetic, electrochemical, in situ Raman, and theoretical analyses reveal that the rational phase boundaries between the microparticles and nanowires contribute to promoting the Li storage activity. Furthermore, a 16.0 cm2 all-FLIB pouch cell assembled based on the ATO/CC/OTO anode and LiNiCoMnO2 cathode coated on ATO/CC (ATO/CC/LNCM) exhibits impressive flexibility under different folding conditions, creating opportunity for the development of high areal capacity anodes in future flexible energy storage devices.

Exploring the relationship between SARS-CoV-2 variants, illness severity at presentation, in-hospital mortality and COVID-19 vaccination in a low middle-income country: A retrospective cross-sectional study.

Background and Aims: COVID-19 morbidity and mortality varied globally through the pandemic. We studied the relationship of SARS-CoV-2 variants of concern (VOC) with COVID-19 severity and mortality among hospitalized patients in Pakistan. Methods: A retrospective review of clinical, laboratory, and vaccination data of 197 COVID-19 adult patients at the Aga Khan University Hospital, Karachi between April 2021, and February 2022 was performed. SARS-CoV-2 VOC identified in respiratory samples were analyzed. Univariate and multivariate analysis was conducted to identify factors associated with COVID-19 outcomes. Results: The median age of cases was 55 years and 51.8% were males. Twenty-four percent of females were pregnant. Of COVID-19 cases, 48.2% had nonsevere disease, while 52.8% had severe/critical disease. Hypertension (48%) and diabetes mellitus (41%) were common comorbids. SARS-CoV-2 VOC identified comprised; Omicron (55.3%), Beta (14.7%), Alpha (13.7%), Delta (12.7%), and Gamma (3.6%) variants. Most (59.7%) study subjects were unvaccinated. Of vaccines, 88% had received inactivated virus COVID-19 vaccines. Increased risk of severe disease was associated with age ≥50 years (odds ratio [OR]: 5.73; 95% confidence interval [CI]: [2.45-13.7]), as well as with diabetes mellitus (OR: 4.24; 95% CI: [1.82-9.85]). Full vaccination (OR: 0.25; 95% CI: [0.11-0.58]) or infection with Omicron (OR: 0.42; 95% CI: [0.23-0.74]) was associated with reduced disease severity. The risk of mortality increased with age ≥50 years (OR: 5.07; 95% CI: [1.92-13.42]) and a history of myocardial infarction (OR: 5.11; 95% CI: [1.45-17.93]) whilst, infection with Omicron was found to reduce the risk (OR: 0.22; 95% CI: [0.10-0.53]). Conclusion: Our study describes the relationship between the severity of COVID-19, in-hospital mortality in relation to SARS-CoV-2 variants, and the impact of COVID-19 vaccination in Pakistan. Outcomes were more favorable in younger individuals, after vaccinations and with Omicron variant infections. Most cases received inactivated virus vaccines therefore these data highlight the protection provided against severe COVID-19.

Diuretic Potential of Fenchyl Acetate with Its Mechanism of Action: Toxicity Study.

Hypertension has become a global threat and is one of the greatest risk factors for chronic kidney disease. Fenchyl acetate is a monoterpene that has been assessed for its various pharmacological activities in the past, but no study has evaluated its diuretic potential and the mechanism involved in the diuretic activity after prolonged administration in rats. Therefore, this study aimed to measure the safety and diuretic profile of fenchyl acetate in rats. For evaluating the acute toxicity, a single dose of 2000 mg/kg was administered as per the OECD guideline no. 425, and the rats were observed for 14 days. After 14 days, blood samples were assessed for biochemical, hematological, and oxidative stress parameters. For the acute diuretic study, fenchyl acetate was given in doses of 100, 200, and 400 mg/kg, and urine samples after 8 h were assessed for sodium, potassium, creatinine, uric acid excretion, and urinary output. A single dose of fenchyl acetate (F.A) was selected for prolonged diuretic activity, and furosemide was taken as the standard drug in a repeated dose administration for 7 days. Rats' urine was assessed for pH, sodium, potassium, creatinine, and uric acid excretion along with urinary volume excretion. Furthermore, blood was withdrawn by cardiac puncture, and selected organs like the heart, liver, kidney, and spleen were analyzed for oxidative stress biomarkers. Using pharmacological antagonists or inhibitors, the involvement of L-NAME, acetylcholine, or prostaglandin in F.A.-induced diuresis was determined. Mitochondrial respiratory chain enzyme complexes were also assessed in the kidney homogenates. The acute toxicity results showed F.A to be safe as its LD50 was greater than 2000 mg/kg and there were no signs of mortality or toxicity. The acute diuretic study showed that F.A resulted in a significant and dose-dependent increase in sodium, potassium, creatinine, and uric acid excretion along with urinary output, and these results were comparable to the standard drug furosemide. Prolonged administration with F.A (400 mg/kg) resulted in a comparable excretion of sodium, potassium, creatinine, uric acid, and urine output with furosemide (15 mg/kg). The oxidative stress parameters revealed that F.A (400 mg/kg) resulted in reducing the formation of free radicals. The results from the mechanism-based studies showed the involvement of NO in inducing diuresis. Furthermore, F.A (400 mg/kg) significantly increased the mitochondrial complexes I, II, III, IV, I + III, and II + III in the kidney homogenates, thus restoring the mitochondrial enzymes and improving the renal function. The current study suggests that F.A is safe with a significant diuretic potential with the involvement of NO in its mechanism of action.

Mechanistic Evaluation of Antiarthritic Effects of Citronellol in CFA-Induced Arthritic Rats.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation, joint tissue damage, pain, and synovitis. It leads to deformity of joints, disability, and even premature death. Markers of inflammation are highly expressed in synovium fluid and serum of arthritic patients and play an important role in the pathophysiology of RA. These transcription factors promote the fabrication of type I interferons and inflammatory cytokines. In RA, degradation of synovial cartilage and bone results from stimulation of proinflammatory cytokines. Citronellol (Ct), a monoterpene alcohol, is found in citrus fruits and essential oils of many aromatic plants. It possesses numerous pharmacological properties such as antioxidant activity and potential antinociceptive and anti-inflammatory effects. Keeping in view the significant anti-inflammatory role of Ct, a trial of 28 days was conducted. Ct was administered orally at three different doses (25, 50, and 100) mg/kg in Freund's adjuvant-induced arthritic rats, and the results were compared with piroxicam, chosen as the standard drug. The antiarthritic activity of the compound was evaluated through measurements of arthritic scoring and plethysmometry before and after treatment. The blood biochemical and hematological parameters and histopathological analyses were performed. Additionally, qPCR was conducted to analyze the mRNA expression levels of TNF-α, IL-1ß, NF-κB, MMP3, IL-6, and IL-4 in the blood. ELISA was performed to evaluate the levels of PGE2. The results demonstrated that Ct showed significant results at all doses, but the highest dose proved to be most significant in terms of decreasing arthritic scoring and paw edema, indicating the antiarthritic potential of Ct. Furthermore, the compound was found to downregulate all the proinflammatory cytokines (TNF-α, IL-1ß, NF-κB, MMP3, and IL-6) and upregulate the anti-inflammatory cytokine (IL-4). The levels of PGE2 were also reduced which further supported the antiarthritic effects of Ct and validated it as a potential antiarthritic candidate.