Forecasting synergistic pathways between rare earth elements, renewable energy, and product and economic complexities in achieving a low-carbon future.

Recent decades have witnessed an unprecedented transformation in the global energy landscape, driven by environmental concerns and the quest for sustainable economic growth. As the world grapples with the urgent need for decarbonization, the utilization of renewable energy technologies with the instrumental role of rare earth elements (REEs) has come to the forefront. However, empirical investigations into their synergistic pathways for product and economic complexities concerning achieving a low-carbon future remain scarce. Therefore, we forecast synergistic pathways between the REE supply, renewable energy, economic and product complexities, and GDP growth using a panel dataset of 11 REE-producing countries from 1990 to 2023. We used Common Correlated Effects and Temporal Causal Models as primary methods to estimate panel long-run elasticities and subsequently forecast mutual causal synergies between the variables. The results indicated that REE supply led to renewable energy and economic growth that further elevated the countries' product and economic complexities rankings. GDP growth increased REE production, economic complexity, and renewable energy directly, and consequently, product complexity and REE production through them. This underscores the positive role of REE production coupled with renewable energy technologies in achieving a low-carbon future based on economic diversification, enhanced industrial capabilities, and technological sophistication.

Potential role of Citrus bergamia flower essential oil against oral pathogens.

BACKGROUND: Oral bacterial infections are difficult to treat due to emergence of resistance against antibiotic therapy. Essential oils are considered emerging alternate therapy against bacterial infections and biofilms. We investigated Citrus bergemia flower essential oil against oral pathogens. METHODS: The essential oil was analsyed using Gas Chromatography(GC-MS), in silico investigations, antioxidant, antimicrobial, antibiofilm and antiquorum sensing assays. RESULTS: Gas Chromatography analysis confirmed presence of 17 compounds including 1,6-Octadien-3-ol,3,7-dimethyl, 48.17%), l-limonene (22.03%) and p-menth-1-ol, 8-ol (7.31%) as major components. In silico analysis showed compliance of all tested major components with Lipinski's rule, Bioavailability and antimicrobial activity using PASS (prediction of activity spectrum of substances). Molecular docking with transcriptional regulators 3QP5, 5OE3, 4B2O and 3Q3D revealed strong interaction of all tested compounds except 1,6-Octadien-3-ol,3,7-dimethyl. All tested compounds presented significant inhibition of DPPH (2,2-diphenyl-1-picrylhydrazyl) (IC50 0.65 mg/mL), H2O2 (hydrogen peroxide) (63.5%) and high FRAP (ferrous reducing antioxidant power) value (239.01 µg). In antimicrobial screening a significant activity (MIC 0.125 mg/mL) against Bacillus paramycoides and Bacillus chungangensis was observed. Likewise a strong antibiofilm (52.1 - 69.5%) and anti-QS (quorum sensing) (4-16 mm) activity was recorded in a dose dependent manner. CONCLUSION: It was therefore concluded that C. bergemia essential oil posess strong antioxidant, antimicrobial and antibiofilm activities against tested oral pathogens.

The use of e-consent in surgery and application to neurosurgery: a systematic review and meta-analysis.

INTRODUCTION: The integration of novel electronic informed consent platforms in healthcare has undergone significant growth over the last decade. Adoption of uniform, accessible, and robust electronic online consenting applications is likely to enhance the informed consent process and improve the patient experience and has the potential to reduce medico-legal ramifications of inadequate consent. A systematic review and meta-analysis was conducted to evaluate the utility of novel electronic means of informed consent in surgical patients and discuss its application to neurosurgical cohorts. METHODS: A review of randomised controlled trials, non-randomised studies of health interventions, and single group pre-post design studies in accordance with the PRISMA statement. Random effects modelling was used to estimate pooled proportions of study outcomes. Patient satisfaction with the informed consent process and patients' gain in knowledge were compared for electronic technologies versus non-electronic instruments. A sub-group analysis was conducted to compare the utility of electronic technologies in neurosurgical cohorts relative to other surgical patients in the context of patient satisfaction and knowledge gain. RESULTS: Of 1042 screened abstracts, 63 studies were included: 44 randomised controlled trials (n = 4985), 4 non-randomised studies of health interventions (n = 387), and 15 single group pre-post design studies (n = 872). Meta-analysis showed that electronic technologies significantly enhanced patient satisfaction with the informed consent process (P < 0.00001) and patients' gain in knowledge (P < 0.00001) compared to standard non-electronic practices. Sub-group analysis demonstrated that neurosurgical patient knowledge was significantly enhanced with electronic technologies when compared to other surgical patients (P = 0.009), but there was no difference in patient satisfaction between neurosurgical cohorts and other surgical patients with respect to electronic technologies (P = 0.78). CONCLUSIONS: Novel electronic technologies can enhance patient satisfaction and increase patients' gain in knowledge of their surgical procedures. Electronic patient education tools can significantly enhance patient knowledge for neurosurgical patients. If used appropriately, these modalities can shorten and/or improve the consent discussion, streamlining the surgical process and improving satisfaction for neurosurgical patients.

Nanocrystals of Mangiferin Using Design Expert: Preparation, Characterization, and Pharmacokinetic Evaluation.

Making nanoscale drug carriers could boost the bioavailability of medications that are slightly water soluble. One of the most promising approaches for enhancing the chemical stability and bioavailability of a variety of therapeutic medicines is liquid nanocrystal technology. This study aimed to prepare nanocrystals of mangiferin for sustained drug delivery and enhance the pharmacokinetic profile of the drug. The fractional factorial design (FFD) was used via a selection of independent and dependent variables. The selected factors were the concentration of mangiferin (A), hydroxypropyl methyl cellulose (HPMC) (B), pluronic acid (C), tween 80 (D), and the ratio of antisolvent to solvent (E). The selected responses were the particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The nanocrystals were further evaluated for mangiferin release, release kinetics, Fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), particle size, zeta potential, and scanning electron microscopy (SEM). The stability studies of developed nanocrystals were performed for 6 months and pharmacokinetics on albino rabbits. The value of entrapment efficiencies ranged from 23.98% to 86.23%. The percentage release of mangiferin varied from 62.45 to 99.02%. FTIR and DSC studies showed the stability of mangiferin in the nanocrystals. The particle size of the optimized formulation was almost 100 nm and -12 mV the value of the zeta potential. The results of stability studies showed that the nanocrystals of mangiferin were stable for a period of six months. The peak plasma concentration of mangiferin from nanocrystals and suspension of mangiferin were 412 and 367 ng/mL, respectively. The value of AUC0-t of nanocrystals and suspension of mangiferin was 23,567.45 ± 10.876 and 18,976.12 ± 9.765 µg×h/mL, respectively, indicating that the nanocrystals of mangiferin showed greater availability of mangiferin compared to the suspension of the formulation. The developed nanocrystals showed a good release pattern of mangiferin, better stability studies, and enhanced the pharmacokinetics of the drug.

Design and Evaluation of Hydrophobic Ion Paired Insulin Loaded Self Micro-Emulsifying Drug Delivery System for Oral Delivery.

Despite several novel and innovative approaches, clinical translation of oral insulin delivery into commercially viable treatment is still challenging due to its poor absorption and rapid degradation in GIT. Thus, an insulin-SDS hydrophobic ion pair loaded self-microemulsifying drug delivery system (SMEDDS) was formulated to exploit the hypoglycemic effects of orally delivered insulin. Insulin was initially hydrophobically ion paired with sodium dodecyl sulphate (SDS) to enhance its lipophilicity. The successful complexation of Insulin-SDS was confirmed by FTIR and surface morphology was evaluated using SEM. Stability of insulin after its release from HIP complex was evaluated using SDS PAGE. Subsequently, Ins-SDS loaded SMEDDS was optimized using two factorial designs. In vitro stability of insulin entrapped in optimized SMEDDS against proteolytic degradation was also assessed. Further, antidiabetic activity of optimized Ins-SDS loaded SMEDDS was evaluated in diabetic rats. Insulin complexed with SDS at 6:1 (SDS/insulin) molar ratio with almost five-fold increased lipophilicity. The SMEDDS was optimized at 10% Labraphil M2125 CS, 70% Cremophore EL, and 20% Transcutol HP with better proteolytic stability and oral antidiabetic activity. An Ins-SDS loaded SMEDDS was successfully optimized. Compared with insulin and Ins-SDS complex, the optimized SMEDDS displayed considerable resistance to GI enzymes. Thus, the SMEDDS showed potential for effective delivery of macromolecular drugs with improved oral bioavailability.

MGMT Promoter Methylation: Prognostication beyond Treatment Response.

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively.

Herbal Formulation Comprised of Methanol Extracts of Tribulus terristris L. and Zingiber officinale Roscoe Has Antihypertensive Effects.

People prefer to use medicinal plants rather than chemical compounds because they are low cost and have fewer adverse events. Zingiber officinale Roscoe is a natural dietary rhizome with anti-oxidative, anti-inflammatory and anti-carcinogenic properties. Tribulus terrestris L. has been used for the treatment of impotence, to enhance sexual drive and performance and for its diuretic and uricosuric effects. The aim of this study was to evaluate the combined effect of 2 extracts, Tribulus terristris and Zingiber officinale (TZ) for antioxidant, enzyme modulation, liver function, kidney function, blood profile and anti-hypertensive effects, which may pave the way for possible therapeutic applications. Antioxidant potential was measured with the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method antioxidant assay (DPPH) and kojic acid was used as the standard drug for tyrosine inhibition assay. The effect of TZ on biochemical parameters of the liver (alanine transferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], total serum protein, total serum albumin, serum bilirubin), kidney (blood urea and creatinine) and hematology (hemoglobin, red blood cells [RBC], platelets, thin-layer chromatography, neutrophils, eosinophils, lymphocytes, monocytes, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) of Wister rats were studied by administering 100, 250 and 500 mg/kg-1 body weight TZ dose orally for 28 days. Antihypertensive effects were measured by the invasive method. The results showed that the scavenging percentage of TZ was 78.5 to 80.4, with an IC50 value of 1166.7 µg/ ml and tyrosinase inhibition was 72% compared with 93% for kojic acid. Different doses (100, 250 and 500 mg/kg) did not show an increase in serum biomarkers of liver and renal parameters. A significant increase in hemoglobin, erythrocytes, hematocrit, white blood cells (WBC) and lymphocytes with no significant increase/decrease in platelet count was observed but blood pressure was significantly decreased. Therefore, we concluded that TZ is safe and can be used in the treatment of hypertension.

Investigating global surface temperature from the perspectives of environmental, demographic, and economic indicators: current status and future temperature trend.

Anthropogenic activities have increased atmospheric concentrations of greenhouse gas emissions, which have observably increased global temperature. Recognizing it as one of the most critical issues caused by human activities, this study investigates the effects of environmental, demographic, and economic indicators on global and regional temperature. For this purpose, advanced and powerful machine learning techniques, such as ANN, CNN, SVM, and LSTM, are employed using the data from 1980 to 2018 of the aforementioned regions to predict and forecast global and regional temperatures in Africa, Asia, Europe, North America, and South America. First, the predicted results were found very close to the actual surface temperature, confirming that environmental, economic, and demographic indicators are critical drivers of climate change. Second, this study forecasted global temperature from 2023 to 2050 and regional temperature from 2022 to 2050. The results also predicted a considerable increase in global temperature and regional temperature in the forthcoming years. Particularly, Asia and Africa may experience extreme weather in the future with an increase of more than 1.6 °C. Based on the findings of this study, the major implications have been that maintaining greenhouse gas emissions, balancing economic development, urbanization, and environmental quality while reducing fossil fuel energy consumption will ensure climate mitigation. The findings demand an alteration in human behavior regarding fossil fuel energy consumption to control greenhouse gas emissions, which is the most significant contributor to climate change.

Prognostic factors and surgical outcomes of spontaneous spinal epidural haematoma: a systematic review and meta-analysis.

Spontaneous spinal epidural haematoma (SSEH) is a rare disease defined as blood accumulation within the vertebral epidural space without a cause identified, which can lead to severe neurological deficits. We aim to provide a comprehensive understanding of the prognostic factors affecting surgical outcomes in true SSEH and propose a critical time frame for operative management. A systematic literature search was performed and registered, using OVID Medline and EMBASE, in line with the PRISMA guidelines. Relevant demographic, clinical, surgical, and outcome data were extracted. The ASIA scale was uniformly used throughout our systematic review. Statistical analysis was performed via logistic regression. Of the 1179 articles examined, we included 181 studies involving 295 adult patients surgically treated for SSEH. SSEH were most commonly found in the cervicothoracic spine, with 2-4 spinal segments most commonly involved. Multivariable logistic regression model showed that the following factors were statistically significant in the post-operative outcome: operation type (P = 0.024), pre-operative neurologic status (P < 0.001), use of warfarin (P = 0.039), and operative interval (P = 0.006). Our retrospective analysis confirms the reversibility of severe neurological deficits after surgical intervention, with a prognosis of post-operative outcomes determined by the use of warfarin, pre-operative ASIA grade, and above all surgical evacuation within 12 h.

Erectile dysfunction: Is platelet-rich plasma the new frontier for treatment in patients with erectile dysfunction? A review of the existing evidence.

Erectile dysfunction (ED) is one of the commonest disorders in adult males and affects 12-19% of men of reproductive age. Only few studies have evaluated the impact of ED on men and couples with infertility-these studies report higher rates of ED in this sub-group of men compared to the general population, with the prevalence of ED in men diagnosed with male infertility ranging from 6.7 to 61.6%. Nevertheless, ED is considered a rare cause of male infertility, accounting for about 0.4-5% of all causes of male infertility. ED remains a poorly treated condition globally and current therapies, like oral medication, offer only temporary symptomatic relief and do not influence disease progression-patients are potentially on lifelong treatment, with ED worsening over time. In contrast, regenerative medicine may potentially reverse or halt the progression of ED processes. In this article, we review the evidence for intracavernosal injections of platelet-rich plasma (PRP) in the treatment of ED.

Determination of antioxidant and bimolecular protective effect of Berberis calliobotrys Aitch. ex Koehne extracts and essential oil against H2O2 induced oxidative damage to pBR 322 DNA and RBCs.

We investigated the protective effect of fractions and essential oil from Berberis calliobotrys on H2O2 induced oxidative damage on pBR322 DNA. The crude plant material was extracted using 90% methanolic and liquid-liquid fractionation was accomplished. The essential oil analysis was performed using GC/MS. The FRAP and DPPH assays were performed to determine antioxidant activity. The DNA protection assay was performed using plasmid pBR 322 DNA. The essential oil analysis indicated presence of germacrene D (9.26%), stearic acid (7.50%), methyl tetradecanoate (6.36%) α-thujene (5.71%) and α-muurolol (5.30%) methyl eugenol (5.17%). In vitro analysis showed significant antioxidant activity of all tested extracts and essential oil. The extract showed significant effects at (1000 µg/mL) on pBR322 DNA. Finally it was concluded that Berberis calliobotrys possesses signifgant protective on effects pBR322 DNA and RBC cellular membrane.

Analgesic and Anti-Inflammatory Properties of Two Hydrogel Formulations Comprising Polyherbal Extract.

Background: Nature represents a basic source of medicinal scaffolds that can develop into potent drugs used in the treatment of many diseases. Aim: The present study was planned to evaluate the combined effects of polyherbal methanolic extract of the herbs (fruit of capsicum, bark of cinnamon, rhizome of turmeric and rhizome of ginger) that were individually well known for their analgesic and anti-inflammatory activities. Furthermore, we aimed to develop hydrogel formulation of this polyherbal extract and to characterize and evaluate its analgesic and anti-inflammatory potential. Materials and Methods: Zingiber officinale (R.), Capsicum annuum (L.), Curcuma longa (L.), and Cinnamomum verum (J.) polyherbal extract (GCTC) was prepared by maceration and evaluated for analgesic and anti-inflammatory potential. Then, two different types of hydrogel formulation were prepared. One is pH-based hydrogel in which carbopol-940 was used and the other is temperature-based gel in which methocel-K100 was used as gelling agent. Different concentrations of polyherbal extract (GCTC), at 1%, 3% and 5%, were used in hydrogel formulation. These prepared hydrogel formulations were characterized and evaluated for analgesic and anti-inflammatory potential. Results: Results show that polyherbal extract and all the developed formulations of polyherbal extract (GCTC), at concentrations of 1%, 3% and 5%, have significant analgesic and anti-inflammatory effects with good appearance, homogeneity, spreadability, extrudability and stability. Conclusion: It was concluded from this project that polyherbal extract (GCTC) and its hydrogel have significant analgesic and anti-inflammatory potential.

Malva parviflora Leaves and Fruits Mucilage as Natural Sources of Anti-Inflammatory, Antitussive and Gastro-Protective Agents: A Comparative Study Using Rat Models and Gas Chromatography.

Malva parviflora L., Little mallow, has been traditionally used as an alternative food source. It acts as a medicinal herb containing a potential source of mucilage thus herein; we aimed to assess the toxicity, anti-inflammatory, antitussive and gastro-protective actions of M. parviflora mucilage extracted from its leaves (MLM) and fruit (MFM). Toxicity studies were investigated by in vitro hemolytic assay whereas acute anti-inflammatory and antitussive activities were assessed by carrageenan-induced paw edema and sulphur dioxide induced cough model in rats, respectively. Gastro-protective effects were studied using ethanol induced acute and chronic gastric ulcer rat models. Their metabolic profiles were determined using gas chromatography. The results revealed that MLM and MFM were non-toxic towards human erythrocytes and their lethal doses were found to be greater than 5 g/kg. Pretreatment with MLM (500 mg/kg) and MFM (500 mg/kg) significantly reduced the carrageenan-induced paw thickness (p < 0.001). Maximum edema inhibition (%) was observed at 4 h in diclofenac sodium (39.31%) followed by MLM (27.35%) and MFM (15.68%). Animals pretreated with MLM (500 mg/kg) significantly lower the cough frequency in SO2 gas induced cough models in contrast to control. Moreover, MLM at doses of 250 and 500 mg/kg reduced the ethanol induced gastric mucosal injuries in acute gastric ulcer models presenting ulcer inhibition of 23.04 and 38.74%, respectively. The chronic gastric ulcer model MFM (500 mg/kg) demonstrated a remarkable gastro-protective effect showing 63.52% ulcer inhibition and results were closely related to standard drug sucralfate. In both models, MLM and MFM decreased gastric juice volume and total acidity in addition to an increased gastric juice pH and gastric mucous content justifying an anti-secretary role of this mucilage that was further confirmed by histopathological examination. Meanwhile, GC analyses of the mucilage revealed their richness with natural as well as acidic monosaccharides. It is concluded that MLM and MFM can be used therapeutically for the management of inflammation, cough and gastric ulcer.

Design and Characterization of Agarose/HPMC Buccal Films Bearing Ondansetron HCl In Vitro and In Vivo: Enhancement Using Iontophoretic and Chemical Approaches.

The study was aimed at designing and characterizing the ondansetron hydrochloride (OND) bearing agarose (AG), and hydroxypropyl methyl cellulose (HPMC) mucoadhesive buccal films employing glycerol as a plasticizer. The buccal delivery of ondansetron hydrochloride was remarkably boosted by employing physical (iontophoresis) and chemical enhancement approaches (chemical penetration enhancers). To explore the influence of different formulation components, i.e., agarose, hydroxypropyl methyl cellulose (HPMC), and glycerol on various evaluating parameters, i.e., tensile strength, swelling index, ex vivo mucoadhesion time, and subsequently on in vitro drug release, a D-optimal design was opted. A buccal film bearing OND was mounted on bovine buccal mucosa for ex vivo permeation studies and impact of chemical and physical enhancement techniques on the permeation profile was also analysed. A linear release profile was revealed in in vitro drug release of OND over 60 minutes and outcomes ascertained the direct relationship between HPMC content and in vitro drug release and inverse relationship was depicted by AG content. The FTIR and DSC thermal analysis was executed to determine the physicochemical interactions and results exposed no chemical interactions between drug and polymers. The drug (OND) appeared as tiny crystals on smooth film surface during scanning electron microscopy (SEM) analysis. A notable enhancement in permeation flux, i.e., 761.02 µg/min of OND during ex vivo permeation studies was witnessed after the application of current (0.5-1 mA) without any time lag and with enhancement ratio of 3.107. A time lag of 15 minutes, 19 minutes, and 26 minutes with permeation flux of 475.34 µg/min, 399.35 µg/min, and 244.81 µg/min was observed after chemical enhancer pretreatment with propylene glycol, Tween 80, and passive, respectively. Rabbit was employed as the experimental animal for pharmacokinetic studies (in vivo) and cats for pharmacological activity (in vivo), and the results illustrated the enhanced bioavailablity (2.88 times) in the iontophoresis animal group when compared with the rabbits of control group. Likewise, a remarkable reduction in emesis events was recorded in cats of iontophoresis group. Conclusively, the histopathological examinations on excised buccal mucosa unveiled no severe necrotic or cytopathetic outcomes of current.

Jasminum sambac: A Potential Candidate for Drug Development to Cure Cardiovascular Ailments.

Jasminum sambac (L.) is a South Asian folkloric medicinal plant that has traditionally been used to treat cardiovascular problems. The current investigation was meticulously organized to explore the pharmacological foundation for the medicinal uses of J. sambac pertaining to cardiovascular ailments and to investigate the core mechanisms. Mechanistic investigation revealed that crude leaf extract of J. sambac produced ex-vivo vasorelaxant effects in endotheliumintact aorta ring preparation and hypotensive effect was recorded via pressure and force transducers coupled to the Power Lab Data Acquisition System. Moreover; J. sambac showed cardioprotective effects against adrenaline -induced left ventricular hypertrophy in rabbits observed hemodynamic. CK-MB, LDH, troponin, CRP, ALT, AST, ALP levels were shown to be lower in the myocardial infarction model, as were necrosis, oedema, and inflammatory cell recruitment in comparison to control. J. sambac has shown good antioxidant potential as well as prolonged the noradrenaline induced platelet adhesion. The vasorelaxant and cardioprotective effects in both in vivo and ex vivo experiments, which are enabled by activation of muscarinic receptor and/or releasing the nitric oxide and by reducing the adrenaline, induced oxidative stress, justifying its usage in cardiovascular disorders.

Physicochemical, antidiarrheal and antidiabetic potential of super food (Moringa oleifera Lam.).

There is a long history of natural products for the treatment of infections and diseases. The objective of present study was to investigate the organoleptic, microscopic, physico-chemical, phytochemical, antidiarrheal and antidiabetic potential of leaf, flowering bud and stem bark of Moringa oleifera L. Macroscopic, microscopic, physico-chemical parameters and phytochemical screening were carried out. Diarrhea was induced with castor oil (10ml/kg), verapamil (3, 10 and 30mg/kg) were used as standard antidiarrheal drug and extract of Moringa oleifera at (100, 300 and 1000mg/kg) was used for treatment. Alpha glucosidase inhibitory assay was carried out by using acarbose (0.5mM) and extracts (5.0 mg/Ml). Diabetes was induced by alloxan (150mg/kg), while glibenclamide (10mg/kg) was used as standard drug, and extracts (at the doses of 500mg/kg) were used to determine the antidiabetic activity. Results showed the presence of primary and secondary metabolites, treatment at the dose of 1.0g/kg of leaf, flowering bud and stem bark showed 94 ±2.527, 85.42±5.460 and 84.58±6.138% protection respectively whereas verapamil (10mg/kg) showed 94.84±3.27% protection. Alpha glucosidase inhibition of stem bark (0.5mg/ml) was 95.43±1.47 and flowering bud 94.78±1.25 whereas acarbose (5mM) inhibition was 92.23±0.14%. Stem bark and flowering bud extract (500mg/kg) decreases the blood glucose level from 388.5±35.83 to 226.3±47.10 and 322.5±48.35 to 173.8±29.5 respectively whereas glibenclamide (10 mg/kg) decreases the blood glucose level from 320.7±22.9 to 146.3±17.7 and increases the body weight of the experimental animal. It was concluded from the results that stem bark has strong antidiabetic potential while leaves of the plant have promising antidiarrheal effect.

Antihyaluronidase and Alkaline Phosphatase (ALP) Activities of Medicinal Plants to Combat Echis carinatus Venom-Induced Toxicities.

Snakebite is one of the most neglected diseases of developing countries. Deaths due to snakebite envenoming are quite high in Pakistan, and many deaths are caused by Echis carinatus envenomation. Traditional use of medicinal plants against snakebites is a common practice in Pakistan due to countless benefits. The current study was performed with the objective to evaluate eighteen Pakistani medicinal plants inhibitory potential against hyaluronidase and alkaline phosphatase enzymes of Pakistani Echis carinatus venom. Hyaluronidase activity (0.2-1.6 mg/0.1 mL) and alkaline phosphatase activity (0.1-0.8 mg/0.1 mL) were measured in dose-dependent manner. Crude methanolic extracts of medicinal plants were used for in vitro investigation of their inhibitory activity against toxic enzymes. All active plants were fractioned using different solvents and were again analyzed for inhibitory activity of same enzymes. Results indicated all plants were able to neutralize hyaluronidase that Swertia chirayita (Roxb. ex Flem.) Karst., Terminalia arjuna Wight and Arn, Rubia cordifolia Thumb., and Matthiola incana (L.) R.Br. inhibited maximum hyaluronidase activity equivalent to standard reference (p > 0.5). Pakistani medicinal plants are dense with natural neutralizing metabolites and other active phytochemicals which could inhibit hyaluronidase activity of Pakistani Echis carinatus venom. Further advanced studies at molecular level could lead us to an alternative for envenoming of Pakistani Echis carinatus venom.

In vitro Characterization and Release Studies of Combined Nonionic Surfactant-Based Vesicles for the Prolonged Delivery of an Immunosuppressant Model Drug.

BACKGROUND: Cyclosporine A (CsA) is an exceptional immunosuppressant used for the treatment of immune disorders. Niosomal vesicles are promising drug carriers that are formed by self-association of nonionic surfactants and cholesterol in an aqueous phase. The objective of the study was to formulate combined nonionic surfactant based vesicles and to evaluate their in vitro characterization, release studies and in vivo studies. MATERIALS AND METHODS: Five niosomal formulations (F7 to F11) were prepared using the thin film hydration method. The molar ratio of cholesterol and non-ionic surfactant taken was 1:1. In formulation F10, the combination of surfactants Span 20 and Brij 35 was used. The niosomes were characterized by zeta sizer and SEM for particle size analysis, in vitro drug release and stability studies. The pharmacokinetic studies were conducted on healthy albino rabbits. RESULTS: The size of niosome was found in the range of 427.1 nm to 972.3 nm. SEM image of optimized formulations F10 exhibit the spherical nature of niosomal vesicles. DSC thermograms of niosomal formulations exhibited a broadened endothermic peak. The stability study exhibited that all formulations are stable and negligible change of vesicle size and entrapment was observed with time. The percentage drug release was significantly higher as compared to CsA plain dispersion for all niosomal formulations at pH 1.2 and 7.4. The release kinetic behavior showed that all preparations were best described by zero order and can release active ingredient in a sustained manner. The pharmacokinetic data showed the test formulation (F10) possessed greater bioavailability as compared to the reference formulation (CsA aqueous dispersion). CONCLUSION: The formulation F10 demonstrated a comparatively more delayed rate of release with enhanced dissolution as compared to a single surfactant scheme. The F10 formulation can be a remarkable nanotechnology for prolonged delivery of CsA orally with improved dissolution profile and bioavailability.

Studies on effects of umbelliferon derivatives against periodontal bacteria; antibiofilm, inhibition of quorum sensing and molecular docking analysis.

OBJECTIVE: Umbelliferon derivatives are exclusively found in plants of Ferula spp. that are commonly used in curing various health concerns related to oral cavity. Diabetic patient are especially effected with periodontitis and allied complications. METHOD: We investigated various compounds isolated from Ferula narthex exudate against clinical strains obtained from diabetic patients with periodontitis. Further antibiofilm, antiquorum sensing and molecular docking studies and ADMET analysis were performed. RESULTS: The docking target included 2Q0J, 2UV0, 3QP5 and 3QP1. HYDE affinity assessment was performed for the first 30 top ranking docked conformations within these active sites. The binding free energy ΔG, FlexX docking score and the most favorable poses for all the compounds were determined. During in vitro analysis, feselol presented high inhibition of Pseudomonas aeruginosa (MIC 0.01 mg/mL, MBC 0.02 mg/mL). Similarly, Feselol presented significant inhibition against clinical strain S. epidermidis (MIC 0.087 mg/mL, MBC 0.174 mg/mL) and S. aureus (MIC 0.087 mg/mL, MBC 0.087 mg/mL) preceded by 10'-R-acetyl-karatavacinol against S. epidermidis (MIC 0.56 mg/mL, MBC 0.56 mg/mL) and S. aureus (MIC 0.28 mg/mL, MBC 0.28 mg/mL). During antibiofilm inhibition assay, 10' R-acetyl-karatavacinol showed significant inhibition (54% at a final concentration 0.45 mg/mL), whereas slight antiquorum sensing activity was recorded. CONCLUSIONS: The umbelliferon derivatives have significant inhibition of clinical isolates and moderate antibiofilm potential.

SHORT COMMUNICATION-Anticancer activity of Ziziphus mauritiana roots against human breast cancer cell line.

This study was designed to evaluate the anticancer activity of Ziziphus mauritiana roots. The dichloromethane and methanol extracts were prepared and anticancer activity was investigated the by using MTT assay. Human breast cancer cell line (MCF-7) was used in this study. 50µg/ml of dichloromethane extract of the roots of plant exhibited significant anticancer activity (70%) against the breast cancer cell line with IC50 20.34±0.9 using doxorubicin as standard. The study indicated that Ziziphus mauritiana has anticancer activity against MCF-7 cell line.