Co-delivery of paclitaxel and curcumin loaded solid lipid nanoparticles for improved targeting of lung cancer: In vitro and in vivo investigation.

The objective of this study was to develop nanotechnology-mediated paclitaxel (PAC) and curcumin (CUR) co-loaded solid lipid nanoparticles (PAC-CUR-SLNs) for the treatment of lung cancer, which is a leading cause of death worldwide. Around 85 % cases of lungs cancer constitute non-small cell lung cancer (NSCLC). PAC-CUR-SLNs were prepared via high pressure homogenization. The in vitro drug release of PAC-CUR-SLNs was checked followed by their in vitro cytotoxic investigation using adenocarcinomic human alveolar basal epithelial cells (A549) cell lines. Anticancer effects along with side effects of the synergistic delivery of PAC-CUR-SLNs were studied in vivo, using BALB/c mice. PAC-CUR-SLNs were nano sized (190 nm), homogeneously disseminated particles with %IE of both PAC and CUR above 94 %. PAC-CUR-SLNs released PAC and CUR in a controlled fashion when compared with free drug suspensions. The cytotoxicity of PAC-CUR-SLNs was higher than individual drug-loaded SLNs and pure drugs. Moreover, the co-delivery displayed synergistic effect, indicating potential of PAC-CUR-SLNs in lung cancer treatment. In vivo tumor investigation of PAC-CUR-SLNs exhibited 12-fold reduced tumor volume and almost no change in body weight of BALB/c mice, when compared with the experimental groups including control group. The inhibition of tumor rate on day 28 was 82.7 % in the PAC-CUR-SLNs group, which was significantly higher than the pure drugs and monotherapies. It can be concluded that, encapsulating the co-loaded antitumor drugs like PAC-CUR in SLNs may help in improved targeting of the tumor with enhanced anticancer effect.

Recent advances in nanoformulation-based delivery for cancer immunotherapy.

Cancer is one of the leading causes of mortality worldwide, and its treatment faces several challenges. Phytoconstituents derived from recently discovered medicinal plants through nanotechnology potentially target cancer cells via PI3K/Akt/mTOR pathways and exert their effects selectively through the generation of reactive oxygen species through ß-catenin inhibition, DNA damage, and increasing caspase 3/9 and p53 expression. These nanocarriers act specifically against different cancer cell lines such as HT-29, MOLT-4 human leukemia cancer and MCF-7 cell lines SKOV-3, Caov-3, SW-626, HepG2, A-549, HeLa, and MCF-7. This review comprehensively elaborates on the cellular and molecular mechanisms, and therapeutic prospects of various plant-mediated nanoformulations to attain a revolutionary shift in cancer immunotherapy.

An approach to optimizing dietary protein to growth and body composition in walking catfish, Clarias batrachus (Linneaeus, 1758).

Clarias batrachus is a commercially important food fish. In the present study, effect of varying dietary protein levels was evaluated on the survival, growth parameters and proximate composition of C. batrachus. Diets comprising 25%, 30%, 35%, 40%, 45%, and 50% crude protein (CP) were supplied to fish in T1, T2, T3, T4, T5, and T6, respectively, at the rate of 5% of fish body weight for the entire 90 days, twice daily. Size of each stocked C. batrachus was recorded after 15 days. Results revealed 100% survival rate of C. batrachus in all treatments. Significantly highest (P<0.001) mean value of weight gain (g/fish), percent weight gain, daily growth rate, specific growth rate and protein efficiency ratio (PER) in C. batrachus were recorded, reared in T4 by feeding 40% CP in diet. The best FCR value (1.90±0.02) for C. batrachus was obtained in T4 by feeding 40%CP in diet. Mean value of water, ash, fat and protein contents (wet mass) were ranged 74.10-79.23%, 3.12-4.68%, 3.90-4.43% and 13.09-16.79% for C. batrachus in the studied treatment groups. Water content (%) was found significantly (P<0.05) higher in the body of C. batrachus for T1, T2, T3 and T6 than for T4 and T5. Ash was found significantly (P<0.05) higher in the fish reared in T4 and T5. Fat content in the wet body mass of C. batrachus was found significantly higher in T4 and T1. While, significant higher (P<0.05) values of mean protein content was noted in C. batrachus reared in T4 and T5. Body composition of C. batrachus was also categorically affected by body size, however, condition factor showed non-significant correlation in most of the relationships in the present study. Overall, results indicated that feeding appropriate diet (containing 40% CP) to the fish resulted good growth performance, lower FCR and higher protein content in the fish. Present study provides valuable knowledge of optimal dietary protein level in C. batrachus which will help in commercial success of aquaculture.

Challenges of enbloc mid-sacrectomy as redo surgery for sacral chordoma: a case report.

Enbloc Sacrectomy is the procedure of choice for aggressive sacral lesions but not widely practiced in Pakistan, both by Neurosurgeons and Orthopaedic surgeons. Only one case has been mentioned in indexed local literature so far and that too not operated in Pakistan. The case of a 27 year old neurologically intact male is presented. He had a huge residual mass and midline non-healing wound after two attempts at intralesional debulking and one full course of local irradiation. He presented to the Mayo Hospital, Lahore on 29th December 2021 for a redo surgery of sacral chordoma. A marginal excision was achieved utilizing posterior only approach. This case will help to understand the key steps in enbloc mid-Sacrectomy and importance of involving multidisciplinary team for ensuring adequate wound closure.

Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase.

BACKGROUND/AIM: Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations. METHOD: Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively. RESULTS: Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, andQTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 µM, 28.27 ± 1.52 µM, and 22.93 ± 1.63 µM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 µM). CONCLUSION: This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms.

Assessment of heavy metals level in chicken with indeterminate analysis in localities of Lahore, Pakistan.

The poultry industry is a significant source of animal protein, vitamins, and minerals, particularly through the consumption of chicken meat. In order to conduct the study, 100 samples of liver, chicken feed, and drinking water were collected in nearby areas of Lahore. The investigation aims to detect the presence of specific heavy metals in the collected samples. For this purpose, atomic absorption spectroscopy (AAS) was used to detect heavy metals after proper preparation of the samples. The experimentally observed data were analyzed through a novel statistical approach known as neutrosophic statistics. It was observed that copper (Cu), zinc (Zn), and cadmium (Cd) were the most prominent metals detected with contamination above the safe limits (for chicken drinking water (Zn = 23.09±13.67 mg/L, Cu = 3.84±3.04 mg/L, Cd = 0.805±0.645 mg/L, Pb = 0.275±0.095 mg/L, As = 0.982±0.978 mg/L), for chicken feed (Zn = 2.705±0.715 mg/kg, Cu = 1.85±0.53 mg/kg, Cd = 3.065±1.185 mg/kg, Pb = 0.215±0.175 mg/kg, As = 0.68±0.22 mg/kg), and chicken's liver (Zn = 3.93±0.66 mg/kg, Cu = 1.2±0.52 mg/kg, Cd = 0.07±0.05 mg/kg, Pb = 0.805±0.775 mg/kg, As = 1.05±0.8 mg/kg)). Similarly, the statistical analysis leads that the findings emphasize the importance of monitoring and mitigating heavy metal contamination in the poultry industry to ensure the safety and quality of poultry products.

3D printing technology and its revolutionary role in stent implementation in cardiovascular disease.

Cardiovascular disease (CVD), exemplified by coronary artery disease (CAD), is a global health concern, escalating in prevalence and burden. The etiology of CAD is intricate, involving different risk factors. CVD remains a significant cause of mortality, driving the need for innovative interventions like percutaneous coronary intervention and vascular stents. These stents aim to minimize restenosis, thrombosis, and neointimal hyperplasia while providing mechanical support. Notably, the challenges of achieving ideal stent characteristics persist. An emerging avenue to address this involves enhancing the mechanical performance of polymeric bioresorbable stents using additive manufacturing techniques And Three-dimensional (3D) printing, encompassing various manufacturing technologies, has transcended its initial concept to become a tangible reality in the medical field. The technology's evolution presents a significant opportunity for pharmaceutical and medical industries, enabling the creation of targeted drugs and swift production of medical implants. It revolutionizes medical procedures, transforming the strategies of doctors and surgeons. Patient-specific 3D-printed anatomical models are now pivotal in precision medicine and personalized treatment approaches. Despite its ongoing development, additive manufacturing in healthcare is already integrated into various medical applications, offering substantial benefits to a sector under pressure for performance and cost reduction. In this review primarily emphasizes stent technology, different types of stents, highlighting its application with some potential complications. Here we also address their benefits, potential issues, effectiveness, indications, and contraindications. In future it can potentially reduce complications and help in improving patients' outcomes. 3DP technology offers the promise to customize solutions for complex CVD conditions and help or fostering a new era of precision medicine in cardiology.

Mavacamten: A Review of a Novel Therapeutic Approach for Hypertrophic Cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is a heart disease that can cause left ventricular hypertrophy, arrhythmias, heart failure, and sudden cardiac death. Currently, pharmacological treatment is limited and ineffective. Mavacamten (CamzyosTM) is a cardiac myosin inhibitor developed as a therapeutic option to reduce myocardial contractility and restoration of myocardial function. The Food and Drug Administration (FDA) approved the use of Mavacamten in 2022 for HCM symptoms. Clinical studies have proven that Mavacamten can reduce Left Ventricular Outflow Tract (LVOT) involvement, cardiac hypercontraction, and hypertrophy. This review provides an overview of HCM, its pathophysiology, current treatments, synthesis of Mavacamten, and the clinical trials of Mavacamten.

Local CO2 reservoir layer promotes rapid and selective electrochemical CO2 reduction.

Electrochemical CO2 reduction reaction in aqueous electrolytes is a promising route to produce added-value chemicals and decrease carbon emissions. However, even in Gas-Diffusion Electrode devices, low aqueous CO2 solubility limits catalysis rate and selectivity. Here, we demonstrate that when assembled over a heterogeneous electrocatalyst, a film of nitrile-modified Metal-Organic Framework (MOF) acts as a remarkable CO2-solvation layer that increases its local concentration by ~27-fold compared to bulk electrolyte, reaching 0.82 M. When mounted on a Bi catalyst in a Gas Diffusion Electrode, the MOF drastically improves CO2-to-HCOOH conversion, reaching above 90% selectivity and partial HCOOH currents of 166 mA/cm2 (at -0.9 V vs RHE). The MOF also facilitates catalysis through stabilization of reaction intermediates, as identified by operando infrared spectroscopy and Density Functional Theory. Hence, the presented strategy provides new molecular means to enhance heterogeneous electrochemical CO2 reduction reaction, leading it closer to the requirements for practical implementation.

Safety of Clopidogrel vs. Ticagrelor in Dual Antiplatelet Therapy Regimens for High-Bleeding Risk Acute Coronary Syndrome Patients: A Comprehensive Meta-analysis of Adverse Outcomes.

INTRODUCTION: Patients of acute coronary syndrome (ACS) at a high-bleeding risk (HBR) often require dual antiplatelet therapy (DAPT) to reduce the risk of recurrent cardiovascular events. Clopidogrel and ticagrelor are the most commonly used antiplatelet agents in DAPT regimens. However, the safety profiles of these drugs in ACS patients at HBR remain a subject of ongoing debate. AIM: To investigate any difference between the safety of clopidogrel and ticagrelor used as a part of DAPT regimen in ACS patients at HBR. METHODS: A systematic search on PubMed, Cochrane Library, and Google Scholar was conducted to identify experimental and observational studies published up to the knowledge cutoff date in September 2023. Studies comparing the safety of clopidogrel and ticagrelor in ACS patients at HBR were included for analysis. The primary outcomes assessed were major bleeding events, stroke, and myocardial infarction (MI), while secondary outcomes included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical and cerebral events (NACCE). RESULTS: We included a total of 8 observational studies in our meta-analysis. The pooled analysis revealed a statistically significant increase in the risk of MI (pooled RR = 1.43; 95% CI 1.12-1.83; P = 0.005) in the patients using clopidogrel. There were no statistically significant differences in major bleeding events (pooled RR = 0.94; 95% CI 0.82-1.09; P = 0.44), stroke (pooled RR = 1.36; 95% CI 0.86-2.14; P = 0.18), all-cause mortality (pooled RR = 1.17; 95% CI 0.97-1.41; P = 0.10), MACCE (pooled RR = 1.07; 95% CI 0.76-1.50; P = 0.69) and NACCE (pooled RR = 0.95; 95% CI 0.66-1.37; P = 0.78) between the two groups. Subgroup analyses based on region were performed. CONCLUSION: Both drugs are generally safe for treating ACS patients with HBR at baseline, although a higher risk of MI was observed with the use of clopidogrel. Nevertheless, drug choice should factor in regional variations, patient-specific characteristics, cost, accessibility, and potential drug interactions.

Leading report of molecular prevalence of tick borne Anaplasma marginale and Theileria ovis in yaks (Bos grunniens) from Pakistan.

Domestic yak (Bos grunniens) is an economically important feature of the mountainous region of Gilgit-Baltistan in Pakistan where agriculture is restricted and yaks play multiple roles which includes being a source of milk, meat, hides, fuel and power. However little is known about the parasitic infections in Pakistani yaks. Aim of this research was to report the prevalence and genetic diversity of protozoa parasite (Theileria ovis, 18 S rDNA gene was targeted) and an obligate bacterium (Anaplasma marginale, msp-1 gene was amplified) in the blood that was sampled from 202 yaks collected from four districts in Gilgit-Baltistan during January 2023 till January 2024. Results revealed that 6/202 (3%) yaks were of Theileria ovis while 8/202 (4%) were Anaplasma marginale infected. Positive PCR products of both parasites were confirmed by DNA sequencing and their similarity with previously available pathogen sequences was determined by BLAST analysis. Phylogenetic tree indicated that isolates of both parasites displayed genetic. Anaplasma marginale infection varied with the sampling districts and Shigar district had the highest rate of bacterial infection. Cows were significantly more prone to Theileria ovis infection than bulls. Calf and hybrid yaks were more prone to Anaplasma marginale infection. In conclusion, this is the first report that yaks residing the Gilgit-Baltistan region in Pakistan are infected with Theileria ovis and Anaplasma marginale. Similar larger scales studies are recommended in various regions of Gilgit-Baltistan to document the infection rates of these parasites to formulate strategies that will lead to the effective control of these pathogens.

Ascitic Fluid Lactate Level as a Predictor of Mortality in Cirrhotic Patients Having Spontaneous Bacterial Peritonitis (SBP).

Introduction Limited studies are available for predicting mortality in patients with spontaneous bacterial peritonitis (SBP) based on ascitic fluid analysis. Recently, a proposition has been made regarding the role of ascitic fluid lactate as a better prognostic indicator of mortality in cirrhotic patients with SBP. Therefore, we aimed to evaluate the utility of ascitic fluid lactate in predicting mortality in cirrhotic patients with SBP. Methods This was a prospective, observational study that was conducted in the Hepato-Gastroenterology Department of Sindh Institute of Urology and Transplantation (SIUT), Karachi from 1 January 2022 to 31 December 2022. All the patients having liver cirrhosis with ascites, aged between 18 and 65 years, and presenting with fever and/or abdominal pain were recruited in the study in the first six months (i.e., from 1 January 2022 to 30 June 2022) and were followed for six more months for the outcome. However, those patients on dialysis or those with hepatocellular carcinoma, any other malignancy as per a history of solid organ transplant, a history of HIV infection, or those underlying systemic sepsis or infections other than SBP were excluded from the study. The presence or absence of SBP was confirmed by doing the ascitic fluid analysis. Ascitic fluid lactate levels were also requested in each patient. Mortality was assessed at one, two, three, and six months, respectively. All the data were analyzed using SPSS version 23.0. The area under the receiver operating curve (AUROC) was obtained for ascitic fluid lactate for predicting mortality in SBP. At an optimal cutoff, the diagnostic accuracy of ascitic fluid lactate was obtained. Results The total number of cirrhotic patients included in the study was 123. The majority of the patients belong to Child Turcotte Pugh (CTP) class C (n = 88; 71%). Two third of the patients (65.8%; n = 81) had viral hepatitis i.e., hepatitis B, D, and/or C, as the cause of cirrhosis. Overall mortality was observed in 51(41.5%) patients. Ascitic fluid lactate was significantly raised in patients with SBP than in patients with non-SBP (p = 0.004). The AUROC of ascitic fluid lactate was highest at three months (AUROC = 0.88) followed by six months (AUROC = 0.84), two months (AUROC = 0.804), and one month (AUROC=0.773). At an optimal cut-off of more than or equal to 22.4 mg/dl, ascitic fluid lactate had a sensitivity of 84.9%, specificity of 85.7%, positive predictive value (PPV) of 97.3%, negative predictive value of 42.8% with diagnostic accuracy of 85% in predicting overall mortality in patients with SBP. On sub-analysis, the diagnostic accuracy of ascitic fluid lactate was highest at six months followed by at three, two, and one month, respectively. Conclusion Ascitic fluid lactate showed a good diagnostic utility in predicting the overall mortality in patients with SBP with the best diagnostic accuracy in predicting long-term (six months) mortality. However, further studies are required to validate our results.

Molecular prevalence of vector borne bacterial pathogens in the blood samples of wild rodent species trapped from Saudi Arabia.

Order Rodentia is the most speciose among mammals and the members of this order are known to host more than 60 zoonotic diseases and rodents are a potential health threat to humans. This study was designed to report the molecular prevalence and phylogenetic evaluation of various blood borne bacterial pathogens (Anaplasma ovis, Anaplasma phagocytophilum, Anaplasma marginale and Bartonella spp.) in the blood samples of four wild rodent species [Meriones rex (N = 27), Acomys dimidiatus (N = 18), Myomys yemeni (N = 6) and Rattus rattus (N = 3)] that were trapped during August till October 2020 from Al Makhwah governorate in Saudi Arabia. Results revealed by 9/54 (16.6%) rodents amplified Msp4 gene and 2/54 (3.7%) rodents amplified rpoB gene of Anaplasma ovis and Bartonella spp. respectively. Anaplasma phagocytophilum and Anaplasma marginale were not detected among enrolled rodent species. Meriones rex was the most highly infected rodent species. DNA sequencing and BLAST analysis confirmed the presence of Anaplasma ovis and the Bartonella koehlerae in rodent blood samples. Phylogenetic analysis of both pathogens showed that Saudi isolates were clustered together and were closely related to isolates that were reported from worldwide countries. Risk factor analysis revealed that prevalence of both bacterial pathogens was not restricted to a particular rodent species or a rodent sex (P > 0.05). In conclusion, we are reporting for the very first time that Saudi rodents are infected with Anaplasma ovis and rodents can be infected with Bartonella koehlerae. Similar studies at large scale are recommended in all those areas of Saudi Arabia that are unexplored for the incidence and prevalence of bacterial pathogens among the rodents that are living near human dwellings in order to prevent bacterial infections in local people as well as in livestock.

Combined effect of endophytic Bacillus mycoides and rock phosphate on the amelioration of heavy metal stress in wheat plants.

BACKGROUND: Zinc (Zn) and nickel (Ni) are nutrients that are crucial for plant growth; however, when they are present at higher concentrations, they can cause toxicity in plants. The present study aimed to isolate plant growth promoting endophytic bacteria from Viburnum grandiflorum and assess its plant and defense promoting potential alone and in combination with RP in zinc (Zn) and nickel (Ni) toxic soil. The isolated endophytic bacteria were identified using 16s rRNA gene sequencing. For the experiment, twelve different treatments were applied using Zn, Ni, isolated endophytic Bacillus mycoides (Accession # MW979613), and rock phosphate (RP). The Ni, Zn and RP were used at the rate of (100 mg/kg) and (0.2 g/kg) respectively. A pot experiment with three replicates of each treatment was conducted using a complete randomized design (CRD). RESULTS: The results indicated that Ni (T5 = seed + 100 mg/kg Ni and T9 = seed + 100 mg/kg Zn) and Zn concentrations inhibited plant growth, but the intensity of growth inhibition was higher in Ni-contaminated soil. Bacillus mycoides and RP at 100 mg/Kg Zn (T12 = inoculated seed + 100 mg/kg Zn + RP0.2 g/kg.) increased the shoot length, leaf width, protein and sugar content by 57%, 13%, 20% and 34%, respectively, compared to the control. The antioxidant enzymes superoxide dismutases (SOD), peroxidase (POD) were decreased in contaminated soil. Furthermore, Ni and Zn accumulation was inhibited in T11 (seed + 100 mg/kg Zn + RP0.2 g/Kg) and T12 (inoculated seed + 100 mg/kg Zn + RP0.2 g/Kg) by 62 and 63% respectively. The Cu, Ca, and K, contents increased by 128, 219 and 85, Mn, Na, and K by 326, 449, and 84% in (T3 = inoculated seed) and (T4 = inoculated seed + RP 0.2 g/Kg) respectively. CONCLUSIONS: Ni was more toxic to plants than Zn, but endophytic bacteria isolated from Viburnum grandiflorum, helped wheat (Triticum aestivum) plants and reduced the toxic effects of Ni and Zn. The effect of Bacillus mycoides was more prominent in combination with RP which promoted and suppressed heavy-metal toxicity. The reported combination of Bacillus mycoides and RP may be useful for improving plant growth and overcoming metal stress.

Body composition markers are associated with changes in inflammatory markers but not vice versa: A bi-directional longitudinal analysis in a population-based sample.

BACKGROUND AND AIM: Growing body of evidence consistently link obesity and inflammation, Although the direction of the association is still unclear. We aimed to investigate longitudinal associations of body anthropometric, composition and fat distribution parameters with inflammatory markers and vice versa. METHOD AND RESULTS: We used data from 2464 individuals of the SHIP-TREND cohort with a median follow-up of 7 years. Linear regression models adjusted for confounders were used to analyze associations of standardized body composition markers derived from classic anthropometry, bioelectrical impedance analysis (BIA) and magnetic resonance imaging (MRI) at baseline with changes in inflammatory markers (C-reactive protein (CRP), white blood cell (WBC), fibrinogen) and vice versa. Higher level of anthropometric markers at baseline were associated with an increase in the change of inflammatory markers. A 13.5 cm higher waist circumference (WC), 16.0 kg body weight and 7.76 % relative fat mass (FM) at baseline was associated with a change in CRP of 0.52 mg/L (95 % confidence interval [CI]: 0.29 to 0.74), 0.51 mg/L (95 % CI: 0.29; 0.74) and 0.58 mg/L (95 % CI: 0.34; 0.82) respectively. Absolute FM showed the strongest association with changes in serum fibrinogen levels (ß for 8.69 kg higher FM: 0.07 g/L; 95 % CI: 0.05; 0.09). Baseline inflammatory markers were only associated with changes in hip circumference. CONCLUSION: Our study indicates the importance of anthropometric, body composition and fat distribution markers as a risk factor for the development of inflammation. To prevent inflammatory-related complications, important is to take measures against the development of obesity.

Hemodynamic Renal Reserve Response in Conscious Normotensive and Hypertensive Mice.

INTRODUCTION: Renal function may be compromised following recovery from kidney insults. Renal functional reserve (RFR) is a measure of the difference between the kidney's maximum capacity and its baseline function, which helps identify any areas of the kidney with compromised function. Usually, RFR is evaluated using acute volume expansion (AVE), but this is typically done in anesthetized animals, which may not accurately represent the kidney's complete functional capacity. In this study, we have introduced a novel method that enables AVE to be conducted in conscious mice. METHODS: We have implemented this innovative approach in two animal models representing either intact or impaired renal function, specifically utilizing a lower nephron hypertensive model. Mice were implanted with radio-transmitters for mean artery blood pressure (MAP) monitoring during the experiment. After recovery, half of the mice were induced hypertension by right kidney nephrectomy combined with the ligation of the upper branch of the left kidney. For the AVE, a volume equivalent to 5% of the mouse's body weight was administered via intravenous (IV) or intraperitoneal bolus injection. Subsequently, the mice were individually housed in cages covered with plastic wrap. Urine was collected every hour for a total of 3 h for the measurement of urine and sodium excretion. RESULTS: The MAPs for all normotensive mice were consistent throughout the AVE, but it increased 5-16 mm Hg in the hypertensive mice upon AVE. Remarkably, conscious mice exhibited a significantly stronger response to IV-administered AVE when compared to anesthetized mice. This response was evident in the increase in urinary flow, which was approximately 170% and 145% higher in conscious normotensive and hypertensive mice, respectively, compared to their respective baselines. In contrast, anesthetized normotensive and hypertensive mice showed only around a 130% and 100% increase in urinary flow, respectively. Additionally, upon AVE, conscious normotensive mice excreted approximately 47% more sodium than conscious hypertensive mice. In contrast, anesthetized normotensive mice excreted only about 30% more sodium than their anesthetized hypertensive counterparts. CONCLUSION: Performing a kidney stress test with a significant solution load in conscious mice seems to be a superior method for evaluating RFR compared to conducting the test under anesthesia. Assessing kidney clearance while the mice are conscious has the potential to enhance the precision of diagnosing and predicting both acute and chronic kidney diseases.

Silicon-nanoparticles loaded biochar for soil arsenic immobilization and alleviation of phytotoxicity in barley: Implications for human health risk.

Arsenic (As)-induced environmental pollution and associated health risks are recognized on a global level. Here the impact of cotton shells derived biochar (BC) and silicon-nanoparticles loaded biochar (nano-Si-BC) was explored on soil As immobilization and its phytotoxicity in barley plants in a greenhouse study. The barley plants were grown in a sandy loam soil with varying concentrations of BC and nano-Si-BC (0, 1, and 2%), along with different levels of As (0, 5, 10, and 20 mg kg-1). The FTIR spectroscopy, SEM-EDX, and XRD were used to characterize BC and nano-Si-BC. Results revealed that As treatment had a negative impact on barley plant development, grain yield, physiology, and anti-oxidative response. However, the addition of nano-Si-BC led to a 71% reduction in shoot As concentration compared to the control with 20 mg kg-1 of As, while BC alone resulted in a 51% decline. Furthermore, the 2% nano-Si-BC increased grain yield by 94% compared to control and 28% compared to BC. The addition of 2% nano-Si-BC to As-contaminated soil reduced oxidative stress (34% H2O2 and 48% MDA content) and enhanced plant As tolerance (92% peroxidase and 46% Ascorbate peroxidase activity). The chlorophyll concentration in barley plants decreased due to oxidative stress. Additionally, the incorporation of 2% nano-Si-BC resulted in a 76% reduction in water soluble and NaHCO3 extractable As. It is concluded that the use of BC or nano-Si-BC in As contaminated soil for barley resulted in a low human health risk (HQ < 1), as it effectively immobilized As and promoted higher activity of antioxidants.

Unleashing the power of retatrutide: A possible triumph over obesity and overweight: A correspondence.

Background and Aims: Overweight and obesity have become global health challenges with increasing prevalence. Several drugs have received Food and Drug Administration approval for nonsyndromic obesity treatment, but most have limitations, including gastrointestinal side effects and limited weight loss efficacy. Body: Retatrutide, a novel incretin mimetic agent, has shown promise in clinical trials for significant weight reduction. It has demonstrated dosage-dependent pharmacokinetics with favorable safety profiles. The primary focus of this paper is to explore retatrutide and critically assess its clinical trials to justify its use and feasibility while highlighting its shortcomings. This paper also delves into the subject of obesity and its health manifestations. Conclusion: It is expected that the use of retatrutide, a triple agonist, will result in significant weight loss among individuals who are obese or overweight.

Hidden Markov Models based intelligent health assessment and fault diagnosis of rolling element bearings.

Hidden Markov Models (HMMs) have become an immensely popular tool for health assessment and fault diagnosis of rolling element bearings. The advantages of an HMM include its simplicity, robustness, and interpretability, while the generalization capability of the model still needs to be enhanced. The Dempster-Shafer theory of evidence can be used to conduct a comprehensive evaluation, and Stacking provides a novel training strategy. Therefore, the HMM-based fusion method and ensemble learning method are proposed to increase the credibility of quantitative analysis and optimize classifiers respectively. Firstly, vibration signals captured from bearings are decomposed into intrinsic mode functions (IMFs) using ensemble empirical mode decomposition (EEMD), and then the Hilbert envelope spectra of main components are obtained; Secondly, multi-domain features are extracted as model input from preprocessed signals; Finally, HMM-based intelligent health assessment framework and fault diagnosis framework are established. In this work, the life cycle health assessment modeling is performed using a few training samples, the bearing degradation state is quantitatively evaluated, normal and abnormal samples are effectively distinguished, and the accuracy of fault diagnosis is significantly improved.

Biochemical characterization of bioinspired nanosuspensions from Swertia chirayita extract and their therapeutic effects through nanotechnology approach.

Swertia chirayita is used as a traditional medicinal plant due to its pharmacological activities, including antioxidant, antidiabetic, antimicrobial, and cytotoxic. This study was aimed to evaluate the therapeutic efficacy of newly synthesized nanosuspensions from Swertia chirayita through nanotechnology for enhanced bioactivities. Biochemical characterization was carried out through spectroscopic analyses of HPLC and FTIR. Results revealed that extract contained higher TPCs (569.6 ± 7.8 mg GAE/100 g)) and TFCs (368.5 ± 9.39 mg CE/100 g) than S. chirayita nanosuspension, TPCs (500.6 ± 7.8 500.6 ± 7.8 mg GAE/100 g) and TFCs (229.5± 3.85 mg CE/100 g). Antioxidant activity was evaluated through DPPH scavenging assay, and nanosuspension exhibited a lower DPPH free radical scavenging potential (06 ±3.61) than extract (28.9± 3.85). Anti-dabetic potential was assessed throughα-amylase inhibition and anti-glycation assays. Extract showed higher (41.4%) antiglycation potential than 35.85% nanosuspension and 19.5% α-amylase inhibitory potential than 5% nanosuspension. Biofilm inhibition activity against E. coli was higher in nanosuspension (69.12%) than extract (62.08%). The extract showed high cytotoxicity potential (51.86%) than nanosuspension (33.63%). These nanosuspensions possessed enhanced bioactivities for therapeutic applications could be explored further for the development of new drugs.