EfficientRMT-Net-An Efficient ResNet-50 and Vision Transformers Approach for Classifying Potato Plant Leaf Diseases.

The primary objective of this study is to develop an advanced, automated system for the early detection and classification of leaf diseases in potato plants, which are among the most cultivated vegetable crops worldwide. These diseases, notably early and late blight caused by Alternaria solani and Phytophthora infestans, significantly impact the quantity and quality of global potato production. We hypothesize that the integration of Vision Transformer (ViT) and ResNet-50 architectures in a new model, named EfficientRMT-Net, can effectively and accurately identify various potato leaf diseases. This approach aims to overcome the limitations of traditional methods, which are often labor-intensive, time-consuming, and prone to inaccuracies due to the unpredictability of disease presentation. EfficientRMT-Net leverages the CNN model for distinct feature extraction and employs depth-wise convolution (DWC) to reduce computational demands. A stage block structure is also incorporated to improve scalability and sensitive area detection, enhancing transferability across different datasets. The classification tasks are performed using a global average pooling layer and a fully connected layer. The model was trained, validated, and tested on custom datasets specifically curated for potato leaf disease detection. EfficientRMT-Net's performance was compared with other deep learning and transfer learning techniques to establish its efficacy. Preliminary results show that EfficientRMT-Net achieves an accuracy of 97.65% on a general image dataset and 99.12% on a specialized Potato leaf image dataset, outperforming existing methods. The model demonstrates a high level of proficiency in correctly classifying and identifying potato leaf diseases, even in cases of distorted samples. The EfficientRMT-Net model provides an efficient and accurate solution for classifying potato plant leaf diseases, potentially enabling farmers to enhance crop yield while optimizing resource utilization. This study confirms our hypothesis, showcasing the effectiveness of combining ViT and ResNet-50 architectures in addressing complex agricultural challenges.

Characterization of structural changes occurring in insulin at different time intervals at room temperature by surface-enhanced Raman spectroscopy.

BACKGROUND: Insulin storage above the temperature recommended by food and drug administration (FDA) causes decrease in its functional efficacy due to degradation and aggregation of its protein based active pharmaceutical ingredient (API) that results poor glycemic control in diabetic patients. The aggregation of protein causes serious neurodegenerative diseases such as type-2 diabetes, Huntington disease, Parkinson's disease, and Alzheimer's disease. Surface-enhanced Raman spectroscopy (SERS) has been employed for the denaturation study of many proteins at the temperature above the recommendations of food and drug administration (FDA) (above 30 °C) which indicates potential of technique for such studies. OBJECTIVE: SERS along with multivariate discriminating analysis techniques-based analysis of degradation of liquid pharmaceutical insulin protein after regular intervals of time at room temperature to analyze the structural changes in this protein during the storage of insulin pharmaceutical at room temperature. METHODS: Silver nanoparticles (Ag-NPs) prepared by chemical reduction method are used as SERS active substrate for the surface enhancement of the insulin spectral signal. SERS spectral measurements of insulin were collected from eight different samples of insulin in the time range of 7 pm to 7 am first at fridge temperature (5 °C), second after half hour and next six with the time difference of 2 h each time at room temperature. The acquired SERS spectral data was preprocessed and analyzed. SERS structural transformations detection and discrimination potential in insulin was further confirmed by applying multivariate discriminating analysis techniques including principal component analysis (PCA) and Partial least square regression analysis (PLSR). RESULTS: SERS significantly detects the structural changes produced in insulin even after 2 h of insulin placement at room temperature. PCA successfully differentiates the insulin spectral data obtained after regular intervals of time according to PC-1 (77 %) explained variance. Application of PLSR model provides quantitative confirmation of SERS efficiency, by providing insulin data regression coefficients plot, efficient prediction of time with calibration data set having 0.77 mean square absolute error of calibration (RMSAEC), validation data set with 0.80 mean square absolute error of prediction (RMSAEP) and 0.98 coefficient of determination (R2) for both calibration and validation data set. CONCLUSION: SERS is proved as a highly sensitive and discriminating technique to detect and discriminate insulin structural changes after regular intervals of time at room temperature.

Pain Relief Durations of Different Concentrations of Lidocaine in Wide Awake Hand Surgery: A Prospective Randomised Clinical Trial.

OBJECTIVE: This study aims to determine the minimal concentration of lidocaine to provide adequate analgesia in wide awake local anaesthesia no tourniquet (WALANT) hand surgeries comparing 3 dilutions of tumescent lidocaine with epinephrine solution. STUDY DESIGN: A randomised control trial. Place and Duration of the Study: The study was held at the Plastic Surgery Department of Mayo Hospital, Lahore, from September 2020 to March 2021. METHODOLOGY: Inclusion criteria were post-traumatic hand contractures and tendon and nerve injuries. The patients were randomised to 3 groups of 30 each: Group A (0.1% lidocaine), Group B (0.2% lidocaine), and Group C (0.3% lidocaine). The dilution of adrenaline also remained constant at 1:200,000. Pain was measured using the Visual Analogue Scale. The three groups were compared for demographics and the total duration of analgesia in minutes. RESULTS: All groups showed adequate pain relief during surgery with no cases requiring conversion to general anaesthesia. The highest total duration of analgesia was seen in the 0.3% group (805.3±195.2 minutes), followed by the 0.2% group (500.4±87.2 minutes) and 0.1% group (381.3±31.6 minutes) (p<0.05). No patient developed any signs of lidocaine toxicity. A low Lidocaine concentration of 0.1% was effective in providing analgesia during surgery though increasing the lidocaine concentration to 0.3% would result in greater post-operative analgesic time without increasing toxicity. CONCLUSION: Adequate analgesia was recorded with all 3 lidocaine concentrations. The greatest pain-free duration was however observed in the  0.3% lidocaine group. KEY WORDS: Wide awake local anaesthesia no tourniquet (WALANT), Lidocaine concentrations, Hand surgery, Analgesia, Adverse effects.

Intergenerational trauma: A silent contributor to mental health deterioration in Afghanistan.

Multiple theories, including family systems, epigenetics, attachments, and many others, have proposed mechanisms for trauma transmission from generation to generation. Intergenerational trauma is today one of the most important psychosocial issues affecting Afghans' mental health and psychology, with the potential to affect subsequent generations. A variety of factors have impacted the mental health of the Afghan population over the years, including years of conflict, socioeconomic instability, natural disasters, chronic drought conditions, economic turmoil, and food insecurity, all of which have been exacerbated by recent political turbulence and the The Coronavirus pandemic COVID-19 pandemic that has further increased the susceptibility to intergenerational trauma among the Afghan population. International bodies must play a role in addressing intergenerational trauma among Afghans. Breaking the chain in future generations will be possible by resolving political issues, providing adequate health facilities, financial support, and eliminating stigmas associated with mental health issues.

Development of facial palsy following COVID-19 vaccination: A systematic review.

Objective: Reports of facial palsy occurring after the receipt of COVID-19 vaccines have raised concerns but are rare. The purpose of this study is to systematically assess the association between COVID-19 vaccination and facial palsy. Methods: Our systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist and compiled all the reported cases of facial palsy post-COVID-19 vaccination. We discussed the probable pathophysiology behind facial palsy as a consequence of COVID-19 vaccination and measures to be taken for future reference. Furthermore, we conducted a detailed assessment of characteristics, clinical courses, treatment, and recovery of patients with facial palsy after receiving a COVID-19 vaccine. Results: We included 37 studies providing data on 58 individuals in our review. Over half (51.72%) of the patients complained of facial paralysis following the Oxford-AstraZeneca vaccination. Out of 51 cases, most (88.24%) occurred after the 1st dose. The majority (53.45%) of cases had bilateral facial palsy. Intravenous immunoglobin (IVIg), corticosteroids, and plasmapheresis were the first line of treatment with 75.93% of patients partially recovered, including those undergoing treatment or a lack of follow-up till the end while 22.22% had complete symptomatic recovery. Conclusions: Our review shows that Bell's palsy can be a plausible non-serious adverse effect of COVID-19 vaccination. However, the association observed between COVID-19 vaccination and Bell's palsy is less threatening than the COVID-19 infection. Hence, vaccination should be encouraged because facial palsy, if it occurs, has shown favourable outcomes with treatment.

A Homicide in Disguise: How the Autopsy Dug up Clues.

An autopsy is performed in the occurrence of an out-of-the-ordinary manner of death where the cause of death is unclear. Through a detailed medicolegal investigation, it differentiates homicide from suicides or accidents. However, some people do not acknowledge its importance due to the conflict between science and religion. This is especially true for countries with a lack of education and awareness. The family of the deceased may be unmindful of medicolegal matters and hesitate to allow for an autopsy. In the instance that burial takes place before an autopsy was performed, the medicolegal officer requests for an exhumation. It is the act of digging up a body from its grave to be examined in more detail. Such was the case in our study. A dead body was retrieved from a water channel in the Sindh province, assumed to have accidentally drowned. The family held the funeral before an autopsy was performed. Later, suspicions arose surrounding the death, so the body was exhumed. The soft tissues were decomposed and unidentifiable. The examination suggested strangulation owing to the pivotal discovery of a fractured hyoid bone at the tip of the greater horn of the right cornu. Chemical tests came out negative for intoxication. Therefore, the cause of death was concluded to be asphyxia due to throttling, secondary to hyoid bone fracture. Currently, technology was developed to introduce advanced tests in forensic sciences to differentiate multiple causes of drowning. However, the dissatisfactory budget limits forensic experts in their work. There is little use in testing for diatoms to rule out drowning, as it has been proved to show discrepancies sometimes leading to a false-positive result. Hence, alternative methods need to be explored for a more efficient approach to find the cause of death.

Mitochondrial targeted antioxidants, mitoquinone and SKQ1, not vitamin C, mitigate doxorubicin-induced damage in H9c2 myoblast: pretreatment vs. co-treatment.

BACKGROUND: Preconditioning of the heart ameliorates doxorubicin (Dox)-induced cardiotoxicity. We tested whether pretreating cardiomyocytes by mitochondrial-targeted antioxidants, mitoquinone (MitoQ) or SKQ1, would provide better protection against Dox than co-treatment. METHODS: We investigated the dose-response relationship of MitoQ, SKQ1, and vitamin C on Dox-induced damage on H9c2 cardiomyoblasts when drugs were given concurrently with Dox (e.g., co-treatment) or 24 h prior to Dox (e.g., pretreatment). Moreover, their effects on intracellular and mitochondrial oxidative stress were evaluated by 2,7-dichlorofluorescin diacetate and MitoSOX, respectively. RESULTS: Dox (0.5-50 µM, n = 6) dose-dependently reduced cell viability. By contrast, co-treatment of MitoQ (0.05-10 µM, n = 6) and SKQ1 (0.05-10 µM, n = 6), but not vitamin C (1-2000 µM, n = 3), significantly improved cell viability only at intermediate doses (0.5-1 µM). MitoQ (1 µM) and SKQ1 (1 µM) significantly increased cell viability to 1.79 ± 0.12 and 1.59 ± 0.08 relative to Dox alone, respectively (both p < 0.05). Interestingly, when given as pretreatment, only higher doses of MitoQ (2.5 µM, n = 9) and SKQ1 (5 µM, n = 7) showed maximal protection and improved cell viability to 2.19 ± 0.13 and 1.65 ± 0.07 relative to Dox alone, respectively (both p < 0.01), which was better than that of co-treatment. Moreover, the protective effects were attributed to the significant reduction in Dox-induced intracellular and mitochondrial oxidative stress. CONCLUSION: The data suggest that MitoQ and SKQ1, but not vitamin C, mitigated DOX-induced damage. Moreover, MitoQ pretreatment showed significantly higher cardioprotection than its co-treatment and SKQ1, which may be due to its better antioxidant effects.

Elucidation of plasma protein binding, blood partitioning, permeability, CYP phenotyping and CYP inhibition studies of Withanone using validated UPLC method: An active constituent of neuroprotective herb Ashwagandha.

ETHNOPHARMACOLOGICAL RELEVANCE: Withanone (WN), an active constituent of Withania somnifera commonly called Ashwagandha has remarkable pharmacological responses along with neurological activities. However, for a better understanding of the pharmacokinetic and pharmacodynamic behavior of WN, a comprehensive in-vitro ADME (absorption, distribution, metabolism, and excretion) studies are necessary. AIM OF THE STUDY: A precise, accurate, and sensitive reverse-phase ultra-performance liquid chromatographic method of WN was developed and validated in rat plasma for the first time. The developed method was successfully applied to the in-vitro ADME investigation of WN. MATERIAL AND METHODS: The passive permeability of WN was assayed using PAMPA plates and the plasma protein binding (PPB) was performed using the equilibrium dialysis method. Pooled liver microsomes of rat (RLM) and human (HLM) were used for the microsomal stability, CYP phenotyping, and inhibition studies. CYP phenotyping was evaluated using the specific inhibitors. CYP inhibition study was performed using specific probe substrates along with WN or specific inhibitors. RESULTS: WN was found to be stable in the simulated gastric and intestinal environment and has a high passive permeability at pH 4.0 and 7.0 in PAMPA assay. The PPB of WN at 5 and 20 µg/mL concentrations were found to be high i.e. 82.01 ± 1.44 and 88.02 ± 1.15%, respectively. The in vitro half-life of WN in RLM and HLM was found to be 59.63 ± 2.50 and 68.42 ± 2.19 min, respectively. CYP phenotyping results showed that WN was extensively metabolized by CYP 3A4 and1A2 enzymes in RLM and HLM. However, the results of CYP Inhibition studies showed that none of the CYP isoenzymes were potentially inhibited by WN in RLM and HLM. CONCLUSION: The in vitro results of pH-dependent stability, plasma stability, permeability, PPB, blood partitioning, microsomal stability, CYP phenotyping, and CYP inhibition studies demonstrated that WN could be a better phytochemical for neurological disorders.

Novel Tetrahydroquinazolinamines as Selective Histamine 3 Receptor Antagonists for the Treatment of Obesity.

The histamine 3 receptor (H3R) is a presynaptic receptor, which modulates several neurotransmitters including histamine and various essential physiological processes, such as feeding, arousal, cognition, and pain. The H3R is considered as a drug target for the treatment of several central nervous system disorders. We have synthesized and identified a novel series of 4-aryl-6-methyl-5,6,7,8-tetrahydroquinazolinamines that act as selective H3R antagonists. Among all the synthesized compounds, in vitro and docking studies suggested that the 4-methoxy-phenyl-substituted tetrahydroquinazolinamine compound 4c has potent and selective H3R antagonist activity (IC50 < 0.04 µM). Compound 4c did not exhibit any activity on the hERG ion channel and pan-assay interference compounds liability. Pharmacokinetic studies showed that 4c crosses the blood brain barrier, and in vivo studies demonstrated that 4c induces anorexia and weight loss in obese, but not in lean mice. These data reveal the therapeutic potential of 4c as an anti-obesity candidate drug via antagonizing the H3R.

A randomized controlled clinical trial evaluating the efficacy of zoledronate gel as a local drug delivery system in the treatment of chronic periodontitis: A clinical and radiological correlation.

BACKGROUND: This study aimed to evaluate the efficacy of local drug delivery system of zoledronate (ZLN) gel as an adjunct to scaling and root planing (SRP) for the treatment of human periodontal intrabony defects clinically and radiographically. MATERIALS AND METHODS: Forty intrabony defects (three walled and combined defects without involving furcation) in moderate to severely affected forty chronic periodontitis patients (range, 30-50 years) were randomly divided into two groups and treated either with 0.05% ZLN gel (ZLN n = 20; 1 dropout) or placebo gel (control group [CG] n = 20) after SRP. Clinical parameters such as plaque index (PI), gingival index (GI), tooth-specific pocket probing depth (Ts PPD), and clinical attachment levels (TsCAL) were assessed at baseline and at 3 and 6 months using occlusal acrylic stent. Radiographic parameters were assessed at baseline and 6 months, utilizing "ONIS 2.5 PROFESSIONAL" and "SYNGO" software compatible with DentaScan to measure the volumetric bone changes in intrabony defects. RESULTS: In intragroup comparisons, both groups showed significant PI and GI reduction (P < 0.001) after treatment at 3 and 6 months. In intergroup comparisons, Ts PPD reduction and Ts CAL gain were significant only in ZLN at 6 months from both baseline and 3 months. Radiographically, significant reduction in defect depth and buccolingual width with volumetric defect gain of 40.24% ± 7.44% in ZLN compared to insignificant gain of 1.60% ± 4.06% in CG was observed at 6 months. CONCLUSION: ZLN gel applied subgingivally in intrabony defects resulted in significant improvements both clinically and radiographically.

CD44 targeting hyaluronic acid coated lapatinib nanocrystals foster the efficacy against triple-negative breast cancer.

Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer activity due to active targeting to CD44 receptors than the counterparts LPT-NCs and free LPT. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs treatment caused significant retardation of tumor growth and overall increase in animal survival probability because of their higher tumor localization, increased residence time. Our findings clearly suggest that HA coated LPT-NCs formulation enhances the activity of LPT against triple negative breast cancer. It exhibited magnificent therapeutic outcome at low dose thus presenting a strategy to reduce dose administrations and minimize dose related toxicity.

S-Enantiomer of the Antitubercular Compound S006-830 Complements Activity of Frontline TB Drugs and Targets Biogenesis of Mycobacterium tuberculosis Cell Envelope.

A synthetic molecule S006-830, belonging to the class of thiophene-containing trisubstituted methanes, had shown good in vitro and in vivo bactericidal activity against drug-sensitive and drug-resistant Mycobacterium tuberculosis (Mtb). The molecule had also shown good druglike pharmacokinetic properties. However, S006-830 is a racemic mixture of two enantiomers, one of which could possess a better pharmacological profile than the other. We purified both the enantiomers on a chiral column and observed that S-enantiomer has a significantly higher inhibitory and cidal activity against Mtb than the R-enantiomer. Action of S-S006-830 was "synergistic" for rifampicin and "additive" for isoniazid and ethambutol. The combination of S-S006-830 and rifampicin produced 100% kill of Mtb within 8 days. In a chemical proteomics approach using matrix-bound compound to pull down its target protein(s) from Mtb membrane, FabG4 (ß-ketoacyl CoA reductase, EC 1.1.1.100) emerged as the most likely target for S-S006-830. In target validation assays, the compound exhibited 2-fold higher inhibitory concentration for an Mtb construct overexpressing FabG4. In addition, it inhibited mycolic acid biosynthesis and formation of biofilms by Mtb. Molecular docking of S-S006-830 with FabG4 was consistent with the experimental data. These results support the development of S-S006-830 as a novel lead against tuberculosis.

Correction to "S-Enantiomer of the Antitubercular Compound S006-830 Complements Activity of Frontline TB Drugs and Targets Biogenesis of Mycobacterium tuberculosis Cell Envelope".

[This corrects the article DOI: 10.1021/acsomega.7b01281.].

Bioflavonoid hesperetin overcome bicalutamide induced toxicity by co-delivery in novel SNEDDS formulations: Optimization, in vivo evaluation and uptake mechanism.

In the present study, we designed Bicalutamide (BCT) and Hesperetin (HSP) co-loaded self nano-emulsifying drug delivery system (SNEDDS) to encounter the problem of BCT induced toxicity, low solubility, and bioavailability. Optimized BCT-HSP SNEDDS would produce an emulsion of globule size 30.84±1.24nm with a high encapsulation efficiency of BCT (91.29%) and HSP (88.19%), and showed rapid drug release. DPPH assay confirmed the retention of antioxidant potential of HSP in SNEDDS. DCFH-DA confirmed intense green fluorescence in HSP treated groups due to the generation of reactive oxygen species. Thermogravimetric analysis showed the change in the polymorphic form of BCT. After 14days of sub-acute toxicity study, no significant increase (p>0.05) in the hepatotoxicity markers was observed but BCT-HSP SNEDDS significantly decreased (p<0.001) the levels of nephrotoxicity biochemical markers. Additionally, the histopathological study showed that pulmonary fibrosis and alteration in the bowman's by BCT treatment were conquered by co-administration of HSP. BCT-HSP SNEDDS revealed high AUC0-t of BCT (1.23 fold) and HSP (3.42 fold) than aqueous suspension in male Sprague-Dawley rats. The BCT-HSP SNEDDS were absorbed by clathrin-mediated endocytosis and lymphatic transport absorption pathway. Our results proposed that the co-delivery approach may be useful for in vivo management of prostate cancer.

Synthesis and Evaluation of Chirally Defined Side Chain Variants of 7-Chloro-4-Aminoquinoline To Overcome Drug Resistance in Malaria Chemotherapy.

A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methylpiperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.

Phospholipid complexation of NMITLI118RT+: way to a prudent therapeutic approach for beneficial outcomes in ischemic stroke in rats.

Withania somnifera Dunal (Solanaceae) known as Ashwagandha, a popular plant of Indian origin is known to possess tremedous medicinal potential, often used as anti-inflammatory, anti-platelet, antihypertensive, hypoglycemic, hypolipidemic and adaptogenic candidate. Some of its chemotypes developed by CSIR, India includes NMITLI-101, NMITLI-118, NMITLI-128. In this study the investigators have attempted development of a phytosomal complex of NMITLI118RT + (standardized ethanolic extract of a new chemotype of W. somnifera Dunal.), its pharmaceutical characterization and evaluation of its neuro-protective potential against experimenal stroke in rats in continuation with their previous work in this area. The phytosomal complex (NIMPLC) was prepared by following a cohesive optimization design and was characterized on the basis of solubility, dissolution profile, FT-IR, DSC-TGA analysis, zeta potential, physical stability, forced degradation and photolytic degradation. Results were suggestive of a pharmaceutically acceptable formulation. NIMPLC was taken up further for biological evaluation using the middle cerebral artery occlusion (MCAO) model in rats. It could be demonstrated that the beneficial effects of NMITLI118RT + could be augmented by NIMPLC in 1 h pre and 6 h post treatment as was evident from reduction in MDA levels, increment in GSH levels, reduction in neurological deficit (ND) scores and reduction in infarct size. The study could successfully demonstrate the beneficial effects of NIMPLC in brain function restoration following stroke.

A Standardized Chemically Modified Curcuma longa Extract Modulates IRAK-MAPK Signaling in Inflammation and Potentiates Cytotoxicity.

The TLR/IL-1R pathway is a critical signaling module that is misregulated in pathologies like inflammation and cancer. Extracts from turmeric (Curcuma longa L.) enriched in curcumin and carbonyls like turmerones have been shown to exert potent anti-inflammatory effects. The present study evaluated the anti-inflammatory activity, cytotoxic effect and the underlying mechanism of a novel chemically modified, non-carbonyl compound enriched Curcuma longa L. (C. longa) extract (CMCE). CMCE (1 or 10 µg/mL; 14 h) significantly decreased LPS (50-100 ng/mL) induced TNF-α and IL-1ß production in THP-1 cells, human, and mouse whole blood as measured by ELISA. LPS-induced IRAK1, MAPK activation, TLR4 expression, TLR4-MyD88 interaction, and IκBα degradation were significantly reduced in CMCE pre-treated THP-1 cells as assessed by Western blotting. CMCE (30, 100, and 300 mg/kg; 10 days p.o.) pre-treated and LPS (10 mg/kg) challenged Swiss mice exhibited attenuated plasma TNF-α, IL-1ß, nitrite, aortic iNOS expression, and vascular dysfunction. In a PI permeability assay, cell lines derived from acute myeloid leukemia were most sensitive to the cytotoxic effects of CMCE. Analysis of Sub-G1 phase, Annexin V-PI positivity, loss of mitochondrial membrane potential, increased caspase-3, and PARP-1 activation confirmed CMCE induced apoptosis in HL-60 cells. IRAK inhibition also sensitized HL-60 cells to CMCE induced cytotoxicity. The present study defines the mechanism underlying the action of CMCE and suggests a therapeutic potential for its use in sepsis and leukemia.

PEGylated chitosan nanoparticles potentiate repurposing of ormeloxifene in breast cancer therapy.

AIM: Development and optimization of ormeloxifene-loaded PEGylated chitosan nanoparticles (CNPs) for enhancing its literature profound therapeutic activity against breast cancer. METHODS: CNPs were prepared by ionotropic gelation method and characterized. RESULTS: Optimized formulation (CNPs10) had average 304 nm particle size with 0.247 polydispersity index and spherical shape with +31 mV surface charge. CNPs10 had 88.37% entrapment efficiency and 20.93% loading efficiency. CNPs10 demonstrated dose-dependent enhancement in cytotoxicity, cellular uptake, apoptosis, disruption of mitochondrial membrane potential and activation of caspase-3 in breast cancer MDA-MB-231 and MCF-7 cells over free ormeloxifene. In vivo studies divulged improved pharmacokinetic parameters, reduced toxicity, suppressed tumor burden and increased survival in CNPs10-treated female Sprague-Dawley rats. CONCLUSION: PEGylated CNPs enhanced anticancer activity of ormeloxifene.

Chiral Separation of Ormeloxifene Hydrochloride, a Non-steroidal Contraceptive Agent.

Ormeloxifene hydrochloride (Centchroman) is once-a-week non-steroidal oral contraceptive agent marketed in India and other countries. In this study, we report a validated isocratic high-performance liquid chromatographic (HPLC) method for chiral separation of D- and L-ormeloxifene hydrochloride. This method is capable of baseline separation of its D- and L-isomers. HPLC separation was achieved on a Lux 5µ cellulose-1 with a mobile phase comprising hexane, isopropanol, methanol and triethylamine (90:10:1:0.5). Validation parameters such as limit of detection, limit of quantitation, linearity, precision, accuracy, specificity and preformulation studies were conducted according to new guidelines of International Conference on Harmonization.

Neuro-protective potential of a vesicular system of a standardized extract of a new chemotype of Withania somnifera Dunal (NMITLI118RT+) against cerebral stroke in rats.

Withania somnifera Dunal is an Indian medicinal plant with significant pharmacological properties, such as adaptogenic, anti-inflammatory, anti-oxidant, anti-platelet, anti-hypertensive, hypoglycemic and hypolipidemic effects. Several chemotypes of W. somnifera include NMITLI-101, NMITLI-118 and NMITLI-128. The present work elaborates the optimization and development of a liposomal delivery system for efficient delivery of NMITLI118RT+ [a standardized ethanolic extract of a new chemotype of W. somnifera Dunal (NMITLI-118) roots] against cerebral stroke in rats. Liposomal systems were prepared using thin-film hydration method and characterized on the basis of size, zeta potential, physical stability, FT-IR, DSC-TGA analysis and surface morphological studies by TEM. NMITLI118RT+ and its formulations (NMITLI118RT+LF) were evaluated for biological activity utilizing middle cerebral artery occlusion model in rats. The Z average of the developed liposomal formulation was about 142.6 ± 0.09 nm with a zeta potential of -31.20 ± 1.0 mV. Results of TEM revealed spherical particles in the range of 200 nm. The entrapment efficiency was found to be 94.603 ± 2%. The formulation was found to be physically stable over a 3-week period. Results were suggestive of the fact that both NMITLI118RT+ and its delivery system possess significant neuroprotective activity in cerebral ischemia. The liposomal system largely exhibits better performance over NMITLI118RT+ precisely in the post-treatment group. The present studies could elucidate the successful development of a delivery system for NMITLI118RT+ and demonstrate their beneficial neuro-protective potential in overcoming and reversing the consequences of I/R injury following stroke.