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Purpose: To analyze the efficacy of scleral buckling in the hands of vitreo-retina (VR) fellows under training in eyes with retinal detachment associated with retinal dialysis and analyze the patient and retinal characteristics in these eyes., Methods: We carried out a retrospective consecutive case review at a tertiary eye care center in North India. Records of all the patients who had undergone scleral buckling (SB) for retinal dialysis-associated rhegmatogenous retinal detachment by VR fellows (with less than 2 years' experience) between January 2017 and January 2020 were reviewed., Results: Fifty-three eyes of 53 patients with a mean age of 20.77 years were analyzed. Of the patients, 73.58% were males. History of eye trauma was present in 71.69% patients. A total of 21 residents operated these 53 eyes. SB was able to achieve retinal attachment in a single surgery in 84.9% (45/53) eyes. Mean preoperative best corrected visual acuity was 1.9 ± 1.05 log of minimum angle of resolution (logMAR), which improved postoperatively to 1.07 ± 0.72 logMAR ( P < 0.001). Surgical success rate was 85.71% (24/28) in eyes with no proliferative vitreoretinopathy (PVR), 66.66% (2/3) in eyes with PVR-A, 91.66% (11/12) in eyes with PVR-B, and 80% (8/10) in eyes with PVR-C1. Fifty-two eyes had a single dialysis and one eye had two separate dialysis. Six eyes had giant retinal dialysis (dialysis greater than 3 clock hours) and all were due to trauma. Five patients had retinal dialysis in the fellow eye and were diagnosed with bilateral idiopathic retinal dialysis., Conclusion: Scleral buckling is a safe and effective management for retinal dialysis retinal detachment even in the hands of VR fellows under training., (Copyright © 2024 Indian Journal of Ophthalmology.)

Scleral-fixated intraocular lens (SFIOL) is a widely used technique for IOL implantation in patients where capsular support is insufficient. Most surgeons have shifted away from sutured to sutureless SFIOL techniques where haptics of a multifocal IOL are inserted in scleral tunnels/flaps. Large-scale publications have shown wide variation in the refractive status of eyes post-SFIOL even in the best of the hands. This is because even slight variations in the site of scleral flap/tunnel formation and tension on haptics due to the variable length of haptics placed in scleral flaps/tunnels can alter the effective lens position and induce significant residual refractive error, especially cylindrical astigmatism due to IOL tilt. Our technique aims to reduce residual refractive error after SFIOL implantation. This is achieved by using intraoperative aberrometry and adjusting haptics accordingly to achieve minimal refractive error intraoperatively., (Copyright © 2024 Indian Journal of Ophthalmology.)

There is an annual epidemic of viral conjunctivitis at the onset of the monsoon (rainy) season in North India. This affects a large population, with many patients developing ocular symptoms and then getting better without any treatment as there is no specific therapy for adenoviral infections. However, this creates a dangerous situation for patients with operated trabeculectomy with a filtering bleb as conjunctivitis can lead to blebitis and bleb-related endophthalmitis with super-added bacterial/fungal infections. While the viral infection is self-limiting and most patients get well without treatment, urgent medical attention is required if patients with operated trabeculectomy develop this condition. It is important to educate all patients with operated glaucoma about the outbreak of conjunctivitis and explain the danger signs (like redness, sensitivity to light, vision decrease and pain, which require immediate medical attention and initiation of broad-spectrum antibiotics if a delay is anticipated in visiting the hospital., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

The management of diabetes mellitus has undergone remarkable progress with the introduction of cutting-edge technologies in glucose monitoring and artificial pancreas systems. These innovations have revolutionized diabetes care, offering patients more precise, convenient, and personalized management solutions that significantly improve their quality of life. This review aims to provide a comprehensive overview of recent technological advancements in glucose monitoring devices and artificial pancreas systems, focusing on their transformative impact on diabetes care. A detailed review of the literature was conducted to examine the evolution of glucose monitoring technologies, from traditional invasive methods to more advanced systems. The review explores minimally invasive techniques such as continuous glucose monitoring (CGM) systems and flash glucose monitoring (FGM) systems, which have already been proven to enhance glycemic control and reduce the risk of hypoglycemia. In addition, emerging non-invasive glucose monitoring technologies, including optical, electrochemical, and electro-mechanical methods, were evaluated. These techniques are paving the way for more patient-friendly options that eliminate the need for frequent finger-prick tests, thereby improving adherence and ease of use. Advancements in closed-loop artificial pancreas systems, which integrate CGM with automated insulin delivery, were also examined. These systems, often referred to as "hybrid closed-loop" or "automated insulin delivery" systems, represent a significant leap forward in diabetes care by automating the process of insulin dosing. Such advancements aim to mimic the natural function of the pancreas, allowing for better glucose regulation without the constant need for manual interventions by the patient. Technological breakthroughs in glucose monitoring and artificial pancreas systems have had a profound impact on diabetes management, providing patients with more accurate, reliable, and individualized treatment options. These innovations hold the potential to significantly improve glycemic control, reduce the incidence of diabetes-related complications, and ultimately enhance the quality of life for individuals living with diabetes. Researchers are continually exploring novel methods to measure glucose more effectively and with greater convenience, further refining the future of diabetes care. Researchers are also investigating the integration of artificial intelligence and machine learning algorithms to further enhance the precision and predictive capabilities of glucose monitoring and insulin delivery systems. With ongoing advancements in sensor technology, connectivity, and data analytics, the future of diabetes care promises to deliver even more seamless, real-time management, empowering patients with greater autonomy and improved health outcomes.

Phytosomes (phytophospholipid complex) are dosage forms that have recently been introduced to increase the stability and therapeutic effect of herbal medicine. Currently, bioactive herbs and the phytochemicals they contain are considered to be the best remedies for chronic diseases. One promising approach to increase the efficacy of plant-based therapies is to improve the stability and bioavailability of their bio-active ingredients. Phytosomes employ phospholipids as their active ingredients, and use their amphiphilic properties to solubilize and protect herbal extracts. The unique properties of phospholipids in drug delivery and their use in herbal medicines to improve bioavailability results in significantly enhanced health benefits. The introduction of phytosome nanotechnology can alter and revolutionize the current state of drug delivery. The goal of this review is to explain the application of phytosomes, their future prospects in drug delivery, and their advantages over conventional formulations. Please cite this article as: Chauhan D, Yadav PK, Sultana N, Agarwal A, Verma S, Chourasia MK, Gayen JR. Advancements in nanotechnology for the delivery of phytochemicals. J Integr Med. 2024; 22(4): 385-398., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Breast cancer is the most frequently diagnosed disease causing most deaths in women worldwide. Chemotherapy and neo-adjuvant therapy are the standard method of treatment in early stages of breast cancer. However drug resistance in breast cancer limit the use of these methods for treatment. Research focus is now shifted towards identifying natural phytochemicals with lower toxicity. This review illustrates the NF κB interaction with different signaling pathways in normal condition, breast cancer and other cancer and thus represent a potential target for treatment. No reports are available on the action of picrosides on NFκB and its associated proteins for anticancer activity. In the present review, potential interaction of picrosides with NF-κB and its associated proteins is reviewed for anticancer action. Further, an important facet of this review entails the ADMET analysis of Picroside, elucidating key ADMET properties which serves to underscore the crucial characteristics of Picroside as a potential drug for treating breast cancer. Furthermore, in silico analysis of Picrosides was executed in order to get potential binding modes between ligand (Picrosides II) and NFκB., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Competing interests: None declared.

Picrorhiza kurroa, an "Indian gentian," a known Himalayan medicinal herb with rich source of phytochemicals like picrosides I, II, and other glycosides, has been traditionally used for the treatment of liver and respiratory ailments. Picrosides anti-proliferative, anti-oxidant, anti-inflammatory and other pharmacological properties were evaluated in treating triple-negative breast cancer (TNBC). Picroside I and II were procured from Sigma-Aldrich and were analyzed for anti-cancer activity in triple-negative breast cancer (MDA-MB-231) cells. Cell viability was analyzed using MTT and trypan blue assays. Apoptosis was analyzed through DNA fragmentation and Annexin V/PI flow cytometric analysis. Wound healing and cell survival assays were employed to determine the inhibition of invasion capacity and anti-proliferative activity of picrosides in MDA-MB-231 cells. Measurement of intracellular ROS was studied through mitochondrial membrane potential assessment using DiOC6 staining for anti-oxidant activity of picrosides in MDA-MB-231 cells. Both Picroside I and II have shown decreased cell viability of MDA-MB-231 cells with increasing concentrations. IC 50 values of 95.3 µM and 130.8 µM have been obtained for Picroside I and II in MDA-MB-231 cells. Early apoptotic phase have shown an increase of 20% (p < 0.05) with increasing concentrations (0, 50, 75, and 100 µM) of Picroside I and 15% (p < 0.05) increase with Picroside II. Decrease in mitochondrial membrane potential of 2-2.5-fold (p < 0.05) was observed which indicated decreased reactive oxygen species (ROS) generation with increasing concentrations of Picroside I and II. An increasing percentage of 70-80% (p < 0.05) cell population was arrested in G0/G1 phase of cell cycle after Picroside I and II treatment in cancer cells. Our results suggest that Picroside I and II possess significant anti-proliferative and anti-cancer activity which is mediated by inhibition of cell growth, decreased mitochondrial membrane potential, DNA damage, apoptosis, and cell cycle arrest. Therefore, Picroside I and II can be developed as a potential anti-cancer drug of future and further mechanistic studies are underway to identify the mechanism of anti-cancer potential., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetes mellitus (DM) is a long-lasting metabolic non-communicable disease often characterized by an increase in the level of glucose in the blood or hyperglycemia. Approximately, 415 million people between the ages of 20 and 79 years had DM in 2015 and this figure will rise by 200 million by 2040. In a study conducted by CARRS, it's been found that in Delhi the prevalence of diabetes is around 27% and for prediabetic cases, it is more than 46%. The disease DM can be both short-term and long-term and is often associated with one or more diseases like cardiovascular disease, liver disorder, or kidney malfunction. Early identification of diabetes may help avoid catastrophic repercussions because untreated DM can result in serious complications. Diabetes' primary symptoms are persistently high blood glucose levels, frequent urination, increased thirst, and increased hunger. Therefore, DM is classified into four major categories, namely, Type 1, Type 2, Gestational diabetes, and secondary diabetes. There are various oral and injectable formulations available in the market like insulin, biguanides, sulphonylureas, etc. for the treatment of DM. Recent attention can be given to the various nano approaches undertaken for the treatment, diagnosis, and management of diabetes mellitus. Various nanoparticles like Gold Nanoparticles, carbon nanomaterials, and metallic nanoparticles are some of the approaches mentioned in this review. Besides nanotechnology, artificial intelligence (AI) has also found its application in diabetes care. AI can be used for screening the disease, helping in decision-making, predictive population-level risk stratification, and patient self-management tools. Early detection and diagnosis of diabetes also help the patient avoid expensive treatments later in their life with the help of IoT (internet of medical things) and machine learning models. These tools will help healthcare physicians to predict the disease early. Therefore, the Nano drug delivery system along with AI tools holds a very bright future in diabetes care.

Background and Aim: Precancer biomarkers help in early detection and management of oral potentially malignant disorders (OPMDs). Interleukin-1β (IL-1β), a biomarker, is known to be altered in oral submucous fibrosis (OSMF) and oral leukoplakia (OL). Therefore, we evaluated and compared the serum and salivary IL-1β levels in patients with OSMF/oral leukoplakia and in gender- and age-matched healthy individuals., Materials and Methods: An in vivo, prospective, observational study was conducted on 40 subjects. Subjects were divided into two groups with 20 individuals in each group, that is, Group I: OSMF/oral leukoplakia and Group II: control group. Salivary and serum IL-1β levels were quantitatively estimated using enzyme-linked immunosorbent assay (ELISA). The statistical tests used were unpaired t-test and Chi-square test., Results: The serum IL-1β levels were significantly (P 0.001) lesser in Group I in comparison to Group II. The salivary IL-1β levels remained insignificant between both the groups. However, in both the groups, the salivary IL-1β levels were significantly higher compared to the serum IL-1β levels., Conclusion: We found that the serum IL-1β level can be considered as a prospective biomarker for dysplasia, whereas salivary IL-1β alone needs more elaborated studies to account for its application as a potential biomarker in OPMD., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Aims and Background: Delayed suprachoroidal hemorrhage (DSCH) is a vision-threatening complication of intraocular surgeries with a higher prevalence in postglaucoma filtering surgeries. Through these case series of trabeculectomy complicated with DSCH, we aim to emphasize that correction of hypotony (inciting factor) is fundamental for complete resolution and prevention of recurrence., Case Description: All three glaucoma patients underwent trabeculectomy surgery followed by DSCH on postoperative day 1. Drainage of DSCH using a 23 gauge trocar cannula within 48 hours of onset was performed along with exploration for the cause of hypotony. All three patients had satisfactory visual and anatomical outcomes., Conclusion: Early drainage using 23 gauge trocar cannulas gives good results in DSCH. The cause of hypotony must simultaneously be corrected during the drainage of DSCH. Preventive measures against hypotony should be taken while doing glaucoma filtering surgery., Clinical Significance: Surgical exploration for the cause of hypotony must simultaneously be performed during drainage of DSCH. Primary preventive measures against hypotony and bleeding during glaucoma filtering surgeries, like the use of releasable sutures, viscoelastic in the anterior chamber, and discontinuation of anticoagulants, can be done. Early drainage using trocar cannulas gives satisfactory results in DSCH postglaucoma surgeries., How to Cite This Article: Beri N, Verma S, Bukke AN, et al. Early Drainage of Suprachoroidal Hemorrhage Combined with Surgical Correction of Hypotony after Trabeculectomy. J Curr Glaucoma Pract 2024;18(1):23-27., Competing Interests: Source of support: Nil Conflict of interest: None Patient consent statement The author(s) have obtained written informed consent from the patient for publication of the case report details and related images., (Copyright © 2024; The Author(s).)

Aim & Objective: This study evaluates the potential of combining paclitaxel (PTX) and bortezomib (BTZ) for breast cancer therapy. Materials & Methods: The nanoformulation was optimized via Box-Behnken Design (BBD), with method validation adhering to US-FDA guidelines. Results: Multiple reaction monitoring transitions for PTX, BTZ and internal standard were m/z 855.80→286.60, 366.80→226.00 and 179.80→110.00, respectively. Elution done on C18 Luna column with 0.1% FA in MeOH:10 mM ammonium acetate. The size of nanoformulation was 133.9 ± 1.97 nm, PDI 0.19 ± 0.01 and zeta potential -19.20 ± 1.36 mV. Pharmacokinetics showed higher C max for PTX-BTZ-NE (313.75 ± 10.71 ng/ml PTX, 11.92 ± 0.53 ng/ml BTZ) versus free PTX-BTZ (104 ± 13.06 ng/ml PTX, 1.9 ± 0.08 ng/ml BTZ). Conclusion: Future findings will contribute to the treatment of breast cancer using PTX and BTZ.

Background: Cyclooxygenase enzyme is frequently overexpressed in various types of cancer and found to play a crucial role in poor prognosis in cancer patients. In current research, we have reported the new COX-2 inhibitors for cancer treatment using computer-aided drug design and experimental validation., Methods: A total of 12,795 compounds from the different databases were used to screen against the COX-2 enzyme. It perceived three new compounds with better binding affinity to the enzyme. Afterwards, physicochemical properties and in silico bioactivity were assessed for efficacy, safety, and structural features required for binding. The molecules were synthesized and confirmed by spectroscopic techniques. Later on, molecules were evaluated for their anti-cancer activity using MCF-7, MDA-MB-231 and SiHa cancer cell lines., Results: Compound ZINC5921547 and ZINC48442590 (4a, and 4b) reduced the MCF-7, MDA-MB-231, and SiHa cells proliferation potently than parent compounds. The PG-E2 estimation shown, both compounds act through the COX-2 PGE2 axis. Compound 4a and 4b block the cell cycle at G1-S phase and induce cancer cell death., Conclusions: We concluded that compounds 4a and 4b effectively promotes cancer cell death via COX-2 PGE2 axis, and further in vivo studies can be evaluated for development in both compounds as anticancer agents. The compilation of this information will help us to generate better outcome through robust computational methods. The high-quality experimental results may pave the way for identifying effective drug candidates for cancer treatment., (© 2023. The Author(s), under exclusive licence to Tehran University of Medical Sciences.)

Competing Interests: Competing interests: None declared.

Aim: Pancreastatin, a dysglycemic hormone that encourages inflammation and steatosis in a variety of metabolic disorder animal models. The purpose of this study is to determine the effect of the pancreastatin inhibitor PSTi8 on immunometabolic changes in the liver of MCD-induced NASH mice., Main Methods: Methionine and choline-deficient (MCD) diet was used for the development of NASH. Liver enzymes like SGOT, SGPT, and ALP and lipid profiles were also performed in the serum. Further, immunophenotyping study was performed in the liver through flowcytometer. Subsequently, Hematoxylin and Eosin, Picro Sirius Red and Masson's Trichrome staining were done to check the liver morphology and collagen staining, respectively. Inflammatory cytokines were measured through ELISA and gene expression through RT-PCR. The expression of α-SMA was examined using immunohistochemistry and immunofluorescence staining., Key Findings: PSTi8 inhibited the expression of lipogenic genes in the liver and attenuated bad cholesterol, SGOT, SGPT, and ALP in the serum. PSTi8 improved the liver morphology and attenuated collagen deposition. Subsequently, PSTi8 attenuated inflammatory M1-macrophages, CD8 + T, CD4 + T cells and increased anti-inflammatory M2 macrophages, T-reg and eosinophil populations in the liver. It also attenuated the expression of pro-inflammatory genes like Mcp1, Tnfα, and Il6. Apart from this, PSTi8 attenuated the oxidative stress marker, like ROS, and MDA and fibrosis marker α-SMA in the liver. It also decreased the apoptosis and ROS and MDA level in the liver., Significance: Overall, these compressive studies revealed that PSTi8 exhibited beneficial effect on the liver of MCD-induced NASH mice by attenuating inflammation and oxidative stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Abnormal fat accumulation, enhanced free fatty acids (FFA) release, and their metabolites cause insulin resistance (IR) in major glucose-lipid metabolic organs such as skeletal muscle and adipose tissue. However, excessive lipolysis and FFA release from adipose tissue elevate plasma FFA levels leading to oxidative stress and skeletal muscle IR. Indeed, in obese individuals, there is enhanced pro-inflammatory secretion from adipose tissue influencing insulin signaling in skeletal muscles. Here, we investigated the effect of PSTi8 on FFA-induced IR in both in vitro and in vivo models. Palmitate (Pal)-treated 3T3-L1 cells increased lipid accumulation as well as lipolysis, which reduced the insulin-stimulated glucose uptake. PSTi8 treatment significantly prevented Pal-induced lipid accumulation, and release and enhanced insulin-stimulated glucose uptake. It further reduced the release of pro-inflammatory cytokines from Pal-treated 3T3-L1 cells as well as from adipose tissue explants. In addition, PSTi8 treatment decreases M1 surface markers in Pal-treated bone marrow-derived monocytes (BMDM). PSTi8 treatment also significantly enhanced the Pal-mediated reduced skeletal muscle glucose disposal and reduced intracellular oxidative stress. In vitro effect of PSTi8 was consistent with in vivo HFD-fed mice IR model. PSTi8 treatment in HFD-fed mice significantly improved glucose metabolism and enhanced skeletal muscle insulin sensitivity with reduced adiposity and pro-inflammatory cytokines. Taken together, our results support that PSTi8 treatment can protect both adipose and skeletal muscles from FFA-induced IR., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Microtubules are intracellular, filamentous, polymeric structures that extend throughout the cytoplasm, composed of α-tubulin and β-tubulin subunits. They regulate many cellular functions including cell polarity, cell shape, mitosis, intracellular transport, cell signaling, gene expression, cell integrity, and are associated with tumorigenesis. Inhibition of tubulin polymerization within tumor cells represents a crucial focus in the pursuit of developing anticancer treatments., Areas Covered: This review focuses on the natural product and their synthetic congeners as tubulin inhibitors along with their site of interaction on tubulin. This review also covers the developed novel tubulin inhibitors and important patents focusing on the development of tubulin inhibition for cancer treatment reported from 2018 to 2023. The scientific and patent literature has been searched on PubMed, Espacenet, ScienceDirect, and Patent Guru from 2018-2023., Expert Opinion: Tubulin is one of the promising targets explored extensively for drug discovery. Compounds binding in the colchicine site could be given importance because they can elude resistance mediated by the P-glycoprotein efflux pump and no colchicine site binding inhibitor is approved by FDA so far. The research on the development of antibody drug conjugates (ADCs) for tubluin polymerization inhibition could be significant strategy for cancer treatment.

Aromatase enzyme plays a fundamental role in the development of estrogen receptors, and due to this functionality, the enzyme has gained significant attention as a therapeutic for reproductive disorders and cancer diseases. The currently employed aromatase inhibitors have severe side effects whereas our novel aromatase inhibitor is more selective and less toxic, therefore has greater potential to be developed as a drug. The research framework of this study is to identify a potent inhibitor for the aromatase target by profiling molecular descriptors of the ligand and to find a functional pocket in the target by docking and MD simulations. For assessing cellular and metabolic activities as indicators of cell viability and cytotoxicity, in-vitro studies were performed by using the colorimetric MTT assay. Aromatase activities were determined by a fluorometric method. Cell morphology was assessed by phase-contrast light microscopy. Flow cytometry and Annexin V-FITC/PI staining assay determined cell cycle distribution and apoptosis. This study reports that CHEMBL708 (Ziprasidone) is the most promising compound that showed excellent aromatase inhibitory activity. By using better drug design methods and experimental studies, our study identified a novel compound that could be effective as a high-potential drug candidate against aromatase enzyme. We conclude that the compound ziprasidone effectively blocks the cell cycle at the G1-S phase and induces cancer cell death. Further, in-vivo studies are vital for developing ziprasidone as an anticancer agent. Lastly, our research outcomes based on the results of the in-silico experiments may pave the way for identifying effective drug candidates for therapeutic use in breast cancer., (© 2023. Springer Nature Limited.)

The scope of three-dimensional printing is expanding rapidly, with innovative approaches resulting in the evolution of state-of-the-art 3D bioprinting (3DbioP) techniques for solving issues in bioengineering and biopharmaceutical research. The methods and tools in 3DbioP emphasize the extrusion process, bioink formulation, and stability of the bioprinted scaffold. Thus, 3DbioP technology augments 3DP in the biological world by providing technical support to regenerative therapy, drug delivery, bioengineering of prosthetics, and drug kinetics research. Besides the above, drug delivery and dosage control have been achieved using 3D bioprinted microcarriers and capsules. Developing a stable, biocompatible, and versatile bioink is a primary requisite in biofabrication. The 3DbioP research is breaking the technical barriers at a breakneck speed. Numerous techniques and biomaterial advancements have helped to overcome current 3DbioP issues related to printability, stability, and bioink formulation. Therefore, this Review aims to provide an insight into the technical challenges of bioprinting, novel biomaterials for bioink formulation, and recently developed 3D bioprinting methods driving future applications in biofabrication research., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The most prevalent clinical option for treating cancer is combination chemotherapy. In combination therapy, assessment and optimization for obtaining a synergistic ratio could be obtained by various preclinical setups. Currently, in vitro optimization is used to get synergistic cytotoxicity while constructing combinations. Herein, we co-encapsulated Paclitaxel (PTX) and Baicalein (BCLN) with TPP-TPGS 1000 containing nanoemulsion (TPP-TPGS 1000 -PTX-BCLN-NE) for breast cancer treatment. The assessment of cytotoxicity of PTX and BCLN at different molar weight ratios provided an optimized synergistic ratio (1:5). Quality by Design (QbD) approach was later applied for the optimization as well as characterization of nanoformulation for its droplet size, zeta potential and drug content. TPP-TPGS 1000 -PTX-BCLN-NE significantly enhanced cellular ROS, cell cycle arrest, and depolarization of mitochondrial membrane potential in the 4T1 breast cancer cell line compared to other treatments. In the syngeneic 4T1 BALB/c tumor model, TPP-TPGS 1000 -PTX-BCLN-NE outperformed other nanoformulation treatments. The pharmacokinetic, biodistribution and live imaging studies pivoted TPP-TPGS 1000 -PTX-BCLN-NE enhanced bioavailability and PTX accumulation at tumor site. Later, histology studies confirmed nanoemulsion non-toxicity, expressing new opportunities and potential to treat breast cancer. These results suggested that current nanoformulation can be a potential therapeutic approach to effectively address breast cancer therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To analyze the topographic distribution of neovascularization (NV) and capillary nonperfusion (CNP) using ultra-wide field fluorescein angiography (UWFFA) in patients with proliferative diabetic retinopathy (PDR)., Methods: This was a prospective, single-center, observational study in which all patients who presented between March 2019 and December 2020 and satisfied the inclusion criteria were recruited. In our study, patients with treatment-naïve PDR without any fibrovascular proliferation underwent UWFFA. The images were analyzed qualitatively for the topographic distribution of NV and the CNP area was quantified. The number of lesions picked by UWFFA was compared with 7 standard field (7SF) image using overlay of 7SF. The main outcome measure was characteristics of neovascularization, such as the number, location, and area of CNP, measured using UWFFA, which was considered with 95% confidence intervals (CI)., Results: Two hundred and fifty-three eyes of 187 patients with a mean age of 56.03 ± 8 years were included. Mean neovascularization elsewhere (NVE) was 2.91 ± 3.43. Maximum NVEs were seen in the superotemporal (ST; 0.9 ± 1.13) quadrant, followed by the inferotemporal (IT; 0.7 ± 1.08), inferonasal (IN; 0.66 ± 1.02) and superonasal (SN; 0.66 ± 1.01) quadrants. Maximum CNP area was seen in the SN (13.75 ± 8.83 disc diameter square [DD 2 ]) quadrant, followed by the IN (13.48 ± 8.59 DD 2 ), IT (11.34 ± 8.37 DD 2 ), and ST (11.3 ± 8.34 DD 2 ) quadrants. Mean CNP area was maximum in patients with only neovascularization of disc (NVD; 64.99 ± 41.47 DD 2 ), followed by both NVD and NVE (61.37 ± 35.61 DD 2 ), and was minimum in patients with only NVE (36.44 ± 22.03 DD 2 ). Eighty-one (32%) eyes out of 253 had NVE and 189 (75%) out of 253 had CNP area outside 7SF (overlay) of Early Treatment Diabetic Retinopathy Study (ETDRS)., Conclusion: Diabetic NV lesions and CNP areas are distributed asymmetrically throughout the retina and are not restricted to the posterior pole. Compared to conventional 7SF imaging, UWFFA reveals significantly more retinal vascular pathology in patients with PDR.

Withania Somnifera (WS) is a popular nutritional supplement in the USA, Europe, and Asia, known for its pharmacological effects on neurological disorders. However, the bioanalytical method development, validation, and pharmacokinetics of WS NMITLI-118R AF1 biomarkers Withanolide A (WLD A), Withanone (WNONE), Withanolide B (WLD B), Withaferin A (WF A), and 12 Deoxywithastramonolide (12 DEOXY) in rats have not been comprehensively explored. This study aimed to develop and validate a sensitive and selective LC-ESI-MS/MS method for these biomarkers in male Sprague Dawley rats plasma and brain matrix. Rats were divided into eight groups, each containing five rats. A plant extract of NMITLI-118R AF1 at 50 mg/kg was orally administered to the rats for in-vivo pharmacokinetic investigation. All the analytes had a linear calibration curve (r 2  > 0.999), and intra-day and inter-day precision (%) were found in the range of 2.46 - 13.71% and accuracy were within the acceptable range (±15%). The biomarkers of NMITLI-118R AF1 were found stable in in-vitro plasma and simulated gastro-intestinal fluids. The observed (C max ) and (T max ) values for the biomarkers in the systemic circulation were WLD A (5.59 ± 0.34 ng/mL, T max 1.00 ± 0.00 h), WNONE (6.28 ± 0.41 ng/mL, T max 0.95 ± 0.11 h), WLD B (6.45 ± 2.87 ng/mL, T max 0.95 ± 0.11 h), WF A (6.50 ± 0.27 ng/mL, T max 1.00 ± 0.00 h), and 12 DEOXY (5.68 ± 0.39 ng/mL, T max 1.00 ± 0.00 h). In contrast to the old method, our approach exhibits a lower limit of quantification (LLOQ), shorter run time (less than10 min), and enables the detection of WF A and WNONE in fresh rat plasma by other quantitative analysis of mass spectrometry (m/z) [M] + . Shows high sample volumes for both, larger plasma volumes, costlier sample collection techniques dried blood spot (DBS), more expensive solid phase extraction techniques (SPE) and longer analysis time 14 min. Moreover, our method requires a smaller sample volume 10 µL, offers faster analysis time 4 min, and achieves a higher sensitivity 1 ng/mL. This is the first report of a comprehensive study on in-vitro and in-vivo pharmacokinetics of NMITLI-118R AF1 biomarkers, which may aid in further pre-clinical and clinical trial investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Proteoglycans (PGs) are negatively charged macromolecules containing a core protein and single or several glycosaminoglycan chains attached by covalent bond. They are distributed in all tissues, including extracellular matrix (ECM), cell surface, and basement membrane. They are involved in major pathways and cell signalling cascades which modulate several vital physiological functions of the body. They have also emerged as a target molecule for cancer treatment and as possible biomarkers for early cancer detection. Among cancers, breast cancer is a highly invasive and heterogenous type and has become the major cause of mortality especially among women. So, this review revisits the studies on PGs characterization in breast cancer using LC-MS/MS-based proteomics approach, which will be further helpful for identification of potential PGs-based biomarkers or therapeutic targets., Experimental Design: There is a lack of comprehensive knowledge on the use of LC-MS/MS-based proteomics approaches to identify and characterize PGs in breast cancer., Results: LC-MS/MS assisted PGs characterization in breast cancer revealed the vital PGs in breast cancer invasion and progression. In addition, comprehensive profiling and characterization of PGs in breast cancer are efficiently carried out by this approach., Conclusions: Proteomics techniques including LC-MS/MS-based identification of proteoglycans is effectively carried out in breast cancer research. Identification of expression at different stages of breast cancer is a major challenge, and LC-MS/MS-based profiling of PGs can boost novel strategies to treat breast cancer, which involve targeting PGs, and also aid early diagnosis using PGs as biomarkers., (© 2023 Wiley-VCH GmbH.)

Background  In face of a refractory raised intracranial pressure (ICP), surgeons most commonly resort to decompressive craniectomy (DC). Procedure leaves an unprotected brain underlying the craniectomy defect and Monro-Kellie doctrine: disrupted. Different variants of hinge craniotomies (HC) have been used with clinical outcomes comparable to DC as single stage alternatives. However, both DC and every variant of HC have a limit to the achievable volume augmentation and all invariably cause a compression of the cerebral cortex and its vasculature at the craniotomy site. We believe both these limitations adversely affect the outcome. Methods  A team of neuroscientists in Indian Armed Forces Medical Services has been working for the last 9 years toward developing a novel surgical technique that can mitigate both these drawbacks. Desired procedure should take the centripetal pressure exerted by the combination of the tensile strength of the scalp (with or, without an underlying bone flap) and atmospheric pressure off the brain surface while achieving an assured augmentation of intracranial volume that can be optimized on a case-to-case basis. We call it a "step ladder expansive cranioplasty." Results  The distance of the parietal eminence was found to have increased by 10.2 mm on the operated side after expansive cranioplasty. Conclusion  From drawing board to bedside, we have made some progress toward our goal, but it is still far away from completion. More studies are required to fill in the gaps in our knowledge necessary to optimize the various parameters of the surgery. Procedure has promise to be of special role in in war and disaster scenarios., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Raspberry Ketone (RK) and Resveratrol (RSV) are natural phenolic antioxidants and anti-inflammatory agents. However, its combined pharmacokinetic and pharmacodynamics potentials are not reported. The study aims to assess the combined effect of RK with RSV to protect rats from carbon-tetrachloride (CCl4) induced oxidative stress and NASH. The toxicant CCl4 was employed at a concentration of 1 mL/kg as a 1:1 (v/v) mixture with olive oil twice weekly for 6 weeks to induce liver toxicity. Animal treatment was followed for 2 weeks. Silymarin was used as a standard control drug to compare the hepatoprotective effect of RK and RSV. Hepatic histology, oxidative stress, MMP, reduced glutathione (GSH), plasma levels of SGOT, SGPT, and lipid profile (total cholesterol and triglycerides) were measured. Anti-inflammation genes (IL-10), and fibrotic genes (TGF-β) were also examined in liver tissue. Oral administration of combined RK with RSV (50 + 50 mg/kg for 2 weeks) showed significantly more hepatoprotection by significantly decreasing elevated plasma markers and lipid profile than alone RK and RSV (100 mg/kg daily for 2 weeks). It also significantly alleviated the hepatic lipid peroxidation, restoring the activities of GSH levels in the liver. RT-PCR and Immunoblotting studies confirmed that significantly upregulation of anti-inflammation genes and protein expression (MMP-9) ameliorated the disease. Pharmacokinetic studies confirmed more synergistic stability in simulated gastric-intestinal fluids (FaSSGF, FaSSIF) and rat liver microsomes (CYP-450, NADPH oxidation & glucuronidation. Moreover, coadministration of drugs augmented the relative bioavailability, V d/ F (L/Kg), and MRT 0-∞( h), which leads to more efficacy. This pharmacokinetic and pharmacodynamic reveals a new adjuvant therapy for the treatment of steatohepatitis., (© 2023 Wiley Periodicals LLC.)

Cyclooxygenase-2 (COX-2) is a key aspect of the physiology and pathogenesis of various cancer types. Overexpression of this enzyme is responsible for the elevated prostaglandin production and characteristic feature of breast cancer. Inhibition of COX-2 derived prostanoids facilitates anti-inflammatory, analgesic, and antipyretic effects of non-steroid anti-inflammation drugs. The overexpression of COX-2 is associated with inflammation, pain, and fever. The present study provides the updated relevant literature describing the role of well-characterized isoforms of cyclooxygenase with particular emphasis on COX-2, mechanism of action, the effect of the drug, combinatorial drugs, and microarray-based differential expression analysis and network analysis. We have discussed the currently used combinatorial treatments and their challenges in breast cancer. This article is categorized under: Cancer > Computational Models Cancer > Molecular and Cellular Physiology., (© 2023 The Authors. WIREs Mechanisms of Disease published by Wiley Periodicals LLC.)

Elevated plasma glucose concentration, as a consequence of excessive hepatic glucose production, plays a pivotal role in the development of diabetes. A chromogranin A-derived diabetogenic peptide Pancreastatin (PST) enhances hepatic glucose output leading to diabetes. Therefore, here we probed the role of PSTi8, a PST inhibitor in ameliorating diabetes by investigating the effect of high glucose (HG) or PST on glucose metabolism. Further, we also explored the action mechanism of the underlying anti-hyperglycemic effect of PSTi8. PSTi8 treatment rescue cultured L6 and HepG2 cells from HG and PST-induced insulin resistance, respectively. It also enhances insulin receptor kinase activity by interacting with the insulin receptor and enhancing GLUT4 translocation and glucose uptake. Thus, our in-silico and in-vitro data support the PST-dependent and independent activity of PSTi8. Additionally, PSTi8 treatment in streptozotocin-induced diabetic rats improved glucose tolerance by lowering blood glucose and plasma PST levels. Concomitantly, the treated animals exhibited reduced hepatic glucose production accompanied by downregulation of hepatic gluconeogenic genes PEPCK and G6Pase. PSTi8-treated rats also exhibited enhanced hepatic glycogen in line with reduced plasma glucagon concentrations. Consistently, improved plasma insulin levels in PSTi8-treated rats enhanced skeletal muscle glucose disposal via enhanced P-Akt expression. In summary, these findings suggest PSTi8 has anti-hyperglycemic properties with enhanced skeletal muscle glucose disposal and reduced hepatic gluconeogenesis both PST dependent as well as independent., Competing Interests: Declaration of competing interest “No conflict of interest” is declared by all the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Pancreastatin (PST), an anti-insulin peptide derived from chromogranin A. Its levels increase in cases of obesity, which contributes to adipose tissue inflammation and insulin resistance. This study aims to investigate the immunometabolic effect of PST inhibitor (PSTi8) against PST by using in vitro and in vivo finding., Main Methods: 3T3-L1 cells were differentiated with or without PSTi8, and Oil Red O staining was performed. J774A.1 cells were used for macrophage polarization study. The diet-induced obesity and T2DM model was developed in C57BL/6 mice through high-fat diet for 8 weeks. Alzet osmotic pumps were filled with PSTi8 (release rate: 2 mg/kg/day) and implanted in mice for eight weeks. Further, insulin and glucose tolerance tests were performed. Liver and eWAT sections were stained with hematoxylin and eosin. FACS was used to measure mitochondrial ROS and membrane potential, while Oroboros O2k was used to measure oxygen consumption rate. Immunocytochemistry and qRT-PCR were done for protein and gene expression, respectively., Key Findings: PSTi8 inhibited the expression of lipolytic genes and proteins in 3T3-L1 adipocytes. PSTi8 improved the inulin sensitivity, lipid profile, MMP, and OCR levels in the 3T3-L1 adipocyte and eWAT. It also increased the M1 to M2 macrophage polarization in J77A.1 cells and eWAT. Further, PSTi8 attenuated inflammatory CD4 + T, CD8 + T cells and increased the anti-inflammatory T-reg and eosinophil populations in the eWAT. It also reduced the expression of pro-inflammatory genes like Mcp1, Tnfα, and Il-6., Significance: Collectively, PSTi8 exerted its beneficial effect on adipose tissue inflammation and restored energy expenditure against diet-induced obesity., Competing Interests: Declaration of competing interest All the authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abiraterone acetate (ABRTA) is clinically beneficial in management of metastatic castration-resistant prostate cancer (PC-3). With highlighted low solubility and permeability, orally hampered treatment of ABRTA necessitate high dose to achieve therapeutic efficacy. To triumph these challenges, we aimed to develop intestinal lymphatic transport facilitating lipid-based delivery to enhance bioavailability. ABRTA-containing self-nano emulsified drug delivery (ABRTA-SNEDDS) was statistically optimized by D-optimal design using design expert. Optimized formulation was characterized for particle size, thermodynamic stability, in vitro release, in vivo bioavailability, intestinal lymphatic transport, in vitro cytotoxic effect, anti-metastatic activity, and apoptosis study. Moreover, hemolysis and histopathology studies have been performed to assess pre-clinical safety. Nano-sized particles and successful saturated drug loading were obtained for optimized formulation. In vitro release upto 98.61 ± 3.20% reveal effective release of formulation at intestinal pH 6.8. ABRTA-SNEDDS formulation shows enhanced in vivo exposure of Abiraterone (2.5-fold) than ABRTA suspension in Sprague-Dawley rats. In vitro efficacy in PC-3 cell line indicates 3.69-fold higher therapeutic potential of nano drug delivery system. Hemolysis and histopathology study indicates no significant toxicities to red blood cells and tissues, respectively. Apparently, an opportunistic strategy to increasing bioavailability of ABRTA via intestinal lymphatic transport will create a viable platform in rapidly evolving chemotherapy. Enhanced translational utility of delivery was also supported through in vitro therapeutic efficacy and safety assessments. HighlightsAbiraterone acetate is a prostate cancer drug, impeded with low bioavailability.ABRTA loaded in self nano emulsifying drug delivery enhanced its bioavailability.Intestinal lymphatic transport played role in enhanced bioavailability of ABRTA.ABRTA-SNEDDS enhanced in vitro cytotoxic activity of ABRTA.ABRTA-SNEDDS found safe in preclinical safety evaluations.

Purpose: To evaluate the outcomes of twenty-seven-gauge (27G) vitrectomy in cases with complex proliferative diabetic retinopathy (PDR)., Methods: This was a retrospective interventional study of eyes that underwent 27G vitrectomy for complex PDR. The demographic profile, history, examination findings, and intraoperative surgical steps (especially use of other instruments such as intravitreal scissors/forceps) were reviewed. All the eyes were followed up for a minimum of 3 months at 1-week, 1-month, and 3-month interval. Visual acuity, intraocular pressure (IOP), and retinal status were documented at every follow-up., Results: Nineteen eyes of 17 patients with complex PDR were included in the study. Seven eyes had tractional retinal detachment involving the macula, three had tractional retinal detachment threatening the macula, one had secondary rhegmatogenous retinal detachment, and eight eyes had nonresolving vitreous hemorrhage along with thick fibrovascular proliferation (FVP) at posterior pole. Anatomical attachment was seen in all cases at the end of follow-up with a single surgery. Visual acuity improved from logMAR 2.5 preoperatively to logMAR 1.01 at 3 months ( P = 0.0003). None of the cases required use of intravitreal scissors/forceps for the removal of FVP. Early postoperative vitreous hemorrhage was seen in two eyes. Hypotony was not seen in any eye, while increased IOP was seen in five eyes., Conclusion: 27G vitrectomy is a safe and effective technique in cases with complex diabetic surgery. Due to smaller size cutter, it offers advantages in the dissection of tissue and is associated with lower incidence of early postoperative hemorrhage., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Oman Ophthalmic Society.)

The present paper deals with the modeling of the COVID-19 via fractal interpolation function (FIF) and the estimation of the dimension of constructed FIF. Further, we determine the adjoint of the fractal operator defined on L 2 space associated with the FIF., Competing Interests: Conflict of interestWe declare that we do not have any conflict of interest., (© The Author(s), under exclusive licence to EDP Sciences, Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: To demonstrate the utility of operating on the temporal trabecular meshwork with in vivo - aqueous angiography demonstrating new aqueous outflow channels., Method: In a patient with primary open angle glaucoma, nuclear sclerosis, and medically uncontrolled intraocular pressure, Indocyanine green aqueous angiography (0.5%) was performed to visualize baseline functional aqueous outflow channels. This was followed by 30 degrees bent needle ab-interno goniectomy in the temporal quadrant, where no aqueous outflow channels were initially visualized. Aqueous angiography was repeated using 2% fluorescein to visualize aqueous outflow channels after bent needle ab-interno goniectomy., Results: Prebent needle ab-interno goniectomy, aqueous angiography revealed functional outflow channels in the nasal quadrant although none were visible in the temporal quadrant. Postbent needle ab-interno goniectomy in temporal quadrant aqueous angiography demonstrated 2 new aqueous outflow channels., Conclusion: In a patient with open angle glaucoma, following temporal quadrant ab-interno goniectomy, the recruitment of aqueous outflow channels was demonstrated using aqueous angiography., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The present research was designed to develop a nanoemulsion (NE) of triphenylphosphine-D-α-tocopheryl-polyethylene glycol succinate (TPP-TPGS 1000 ) and paclitaxel (PTX) to effectively deliver PTX to improve breast cancer therapy. Materials & methods: A quality-by-design approach was applied for optimization and in vitro and in vivo characterization were performed. Results: The TPP-TPGS 1000 -PTX-NE enhanced cellular uptake, mitochondrial membrane depolarization and G 2 M cell cycle arrest compared with free-PTX treatment. In addition, pharmacokinetics, biodistribution and  in vivo live imaging studies in tumor-bearing mice showed that TPP-TPGS 1000 -PTX-NE had superior performance compared with free-PTX treatment. Histological and survival investigations ascertained the nontoxicity of the nanoformulation, suggesting new opportunities and potential to treat breast cancer. Conclusion: TPP-TPGS 1000 -PTX-NE improved the efficacy of breast cancer treatment by enhancing its effectiveness and decreasing drug toxicity.

Pancreastatin (PST) is an endogenous bioactive peptide. PST is generated from chromogranin A (Chga) protein which is released by chromaffin and neuroendocrine cells. PST exhibits diabetogenic effect by antagonizing the action of insulin in adipocytes. The level of PST rises during obesity, resulting in persistent low-grade inflammation in adipocytes. Pancreastatin inhibitor 8 (PSTi8), which is developed by modification of PST sequence which antagonizes the action of PST. In this study, we investigated the immunometabolic effect of PSTi8 in the diet-induced obesity (DIO) model in C57BL/6 mice. Here we found PSTi8 decreased the body weight gain, fat mass and increased the lean mass in (DIO) mice. It also showed reduction of adipocyte hypertrophy in eWAT and lipid accumulation in liver of DIO mice. Immunoprofiling of stromal vascular fraction isolated from eWAT of PTSi8 treated mice showed increased anti-inflammatory M2 macrophages, Eosinophil, T-regulatory cells and reduced pro-inflammatory M1 macrophages, CD4 and CD8 T cell population. Apart from this, PSTi8 also improved the mitochondrial function by decreasing reactive oxygen species and increasing mitochondrial membrane potential, NADPH/NADP ratio and citrate synthase activity in eWAT of DIO mice. It also increased the protein expression of pAMPK, pAKT, Arginase -1 and decreased the expression of MHC-II and iNOS in eWAT of DIO mice. In conclusion, PSTi8 exerted its beneficial effect on restoring energy expenditure by reducing adipose tissue inflammation., Competing Interests: Disclosure statements The authors disclose no potential conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

HER2 is the membrane receptor tyrosine kinase showing overexpression in several human malignancies, particularly breast cancer. HER2 overexpression causes the activation of Ras- MAPK and PI3K/Akt/ NF-κB cellular signal transduction pathways that lead to cancer development and progression. HER2 is, therefore, presumed as one of the key targets for the development of tumor-specific therapies. Several preclinical have been developed that function by inhibiting the HER2 tyrosine kinase activity through the prevention of the dimerization process. Most HER2 inhibitors act as ATP competitors and prevent the process of phosphorylation, and abort the cell cycle progression and proliferation. In this review, the clinical drug candidates and potent pre-clinical newly developed molecules are described, and the core chemical scaffolds typically responsible for anti-HER2 activity are deciphered. In addition, the monoclonal antibodies that are either used in monotherapy or in combination therapy against HER2-positive cancer are briefly described. The identified key moieties in this study could result in the discovery of more effective HER2-targeted anticancer drug molecules and circumvent the development of resistance by HER2-specific chemotherapeutics in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Raspberry ketone (RK), derived from red raspberry fruit ( Rubus idaeus , family Rosaceae), is a reported potent antiobesity agent. This study aims to investigate method development, validation, and in vitro and in vivo pharmacokinetics in rats. Materials & methods: LC-MS/MS was used to conduct method development, validation, stability, and oral PK samples of RK in plasma analyses. Results: RK was highly soluble in Tris buffer and stable in gastrointestinal fluids as well as plasma. Rat liver microsomal stability of RK in phase I and II studies was 84.96 ± 2.39 and 69.98 ± 8.69%, respectively, after 60 min. Intestinal permeability was 4.39 ± 1.37 × 10 -5  cm/s. Maximal concentration was 1591.02 ± 64.76 ng/ml, which was achieved after 1 h (time to maximal concentration), and absolute oral bioavailability was 86.28%. Conclusion: Pharmacokinetic data serve as a keystone for preclinical and clinical adjuvant therapy.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Prcis: Human corneoscleral rims provide a low cost model and resource to enhance angle based glaucoma surgical training skills., Purpose: To understand the feasibility, utility, and efficacy of a low-cost model for performing anterior chamber angle gonioscopy and micro-surgery on human corneoscleral tissues in wet lab on resident skill enhancement., Methods: Post-keratoplasty residual corneoscleral rims and/or the expired donor corneoscleral buttons were included for the purpose of this study. Initially, inverted rims were used to demonstrate the basic angle anatomy on a slit lamp bio-microscope. Central hazy cornea was then replaced with an artificial cornea and an artificial anterior chamber to simulate indirect gonioscopy, direct gonioscopy, goniotomy, and other angle-based surgeries. Direct gonioscopy and goniotomy exercises (as a means to simulate intraoperative gonioscopy and other angle-based surgeries respectively) were evaluated quantitatively, and the rest qualitatively., Results: A total of 65 residents were included in the exercise. The mean age was 26.69±1.74 years. Amongst these, 55 ophthalmology residents performed the basic examination, that is, slit lamp mounted angle anatomy examination (n=55) and artificial chamber mounted indirect gonioscopic examination through artificial cornea (n=55). In the second exercise, 10 glaucoma fellows performed the direct gonioscopic and the goniotomy exercises on artificial chamber. The fellows demonstrated a statistically significant improvement in interpretation and surgical skill enhancement concurrent with reduction in time taken with increasing number of attempts ( P <0.05). In the third simulation exercise, micro-stent placement within the Schlemm's canal, subconjunctival space, and the suprachoroidal space was re-produced successfully on multiple occasions., Conclusions: The residual human corneoscleral rims proved to be an important resource for teaching both the basic examination skills and those required for transitioning to advanced intraoperative gonioscopy and goniotomy skills. These low cost, easy to adapt models can be incorporated within the curriculum for improved glaucoma training of both the residents and the glaucoma fellows., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Global hunger and nutritional deficiency demand the advancement of existing and conventional approaches to food production. The application of nanoenabled strategies in agriculture has opened up new avenues for enhancing crop yield and productivity. Recently, two-dimensional (2D) nanomaterials (NMs) have manifested new possibilities for increasing food production and nutrition. Graphene nanosheets, the 2D form of graphene has been exemplary in enhancing the loading capacity of agro-active ingredients, their target-specific delivery, bioavailability, and controlled release with slow degradation, resulting in the increased shelf-life/active time of the agro-active components. Also, the development of novel formulations/composites of MXenes and Transition Metal Dichalcogenides (TMDs) can foster plant growth, metabolism, crop production, protection and improvement of soil quality. Additionally, the 2D NM-based biosensors can monitor the nutrient levels and other parameters affecting agronomical traits in plants. This review provides an insight into the details of 2D NM synthesis and functionalization methods. Notably, the review highlights the broad-range of 2D NM applications and their suitability in the development of nanotechnology-based agriformulations. The 2D NM-based derivatives have shown immense potential in enhancing the pedologic parameters, crop productivity, pest-protection and nutritional value. Thus, assisting in achieving food and environmental sustainability goals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Glaucoma is one of the leading causes of irreversible blindness in the world. Although numerous factors have been implicated in the pathogenesis of glaucoma, the main focus of management still remains lowering the intraocular pressure (IOP) by medical or surgical therapy. However, a major challenge is that many glaucoma patients continue to progress despite good control of IOP. In this regard, the importance of other coexisting factors that may contribute to disease progression needs to be explored. Ophthalmologists need to be aware of ocular risk factors and the impact of systemic diseases and their medications, along with lifestyle modifications on the course of glaucomatous optic neuropathy and adopt a holistic approach in treating the eye as well as the patient to alleviate the suffering from glaucoma in a comprehensive manner., How to Cite This Article: Dada T, Verma S, Gagrani M, et al. Ocular and Systemic Factors associated with Glaucoma. J Curr Glaucoma Pract 2022;16(3):179-191., Competing Interests: Source of support: Nil Conflict of interest: Dr Tanuj Dada and Dr Shibal Bhartiya are associated as the Editorial board members of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of these Editorial board members and their research group., (Copyright © 2022; The Author(s).)

Glutamate-gated chloride channels (GluCls) are unique to invertebrates and are targeted by macrocyclic lactones. In this study, we cloned an AVR-14B GluCl subunit from adult Brugia malayi , a causative agent of lymphatic filariasis in humans. To elucidate this channel's pharmacological properties, we used Xenopus laevis oocytes for expression and performed two-electrode voltage-clamp electrophysiology. The receptor was gated by the natural ligand L-glutamate (effective concentration, 50% [ EC 50 ] = 0.4 mM) and ivermectin (IVM; EC 50 = 1.8 nM). We also characterized the effects of nodulisporic acid (NA) on Bma -AVR-14B and NA-produced dual effects on the receptor as an agonist and a type II positive allosteric modulator. Here we report characterization of the complex activity of NA on a nematode GluCl. Bma -AVR-14B demonstrated some unique pharmacological characteristics. IVM did not produce potentiation of L-glutamate-mediated responses but instead, reduced the channel's sensitivity for the ligand. Further electrophysiological exploration showed that IVM (at a moderate concentration of 0.1 nM) functioned as an inhibitor of both agonist and positive allosteric modulatory effects of NA. This suggests that IVM and NA share a complex interaction. The pharmacological properties of Bma -AVR-14B indicate that the channel is an important target of IVM and NA. In addition, the unique electrophysiological characteristics of Bma -AVR-14B could explain the observed variation in drug sensitivities of various nematode parasites. We have also shown the inhibitory effects of IVM and NA on adult worm motility using Worminator. RNA interference (RNAi) knockdown suggests that AVR-14 plays a role in influencing locomotion in B. malayi .

Tea ( Camellia sinensis ) has several reported health benefits, including that on bone health attributed to catechins of which the most abundant is epigallocatechin-3-gallate (EGCG). However, several preclinical and clinical studies raise safety concerns about EGCG in tea extract causing acute liver failure. Tea also contains kaempferol, albeit scanty, and it has hepatoprotective and osteogenic effects. Here, we utilized a novel extraction procedure of acid hydrolysis to enhance the osteogenic effect of tea extract while reducing its hepatotoxicity. The resultant extract (USKECSE) has a ~40-fold increase in kaempferol and a 2.5-fold reduction in EGCG content compared with the hydroethanolic extract (USCSE). In a female Sprague Dawley (SD) rat femur osteotomy model, USKECSE (100 mg/kg) but not USCSE promoted bone regeneration. In a rat postmenopausal osteoporosis model induced by bilateral ovariectomy (OVX), USKECSE through an osteogenic mechanism maintained bone mass, strength, and microarchitecture to the levels of ovary-intact rats with no hepatotoxic effect. After a single oral dose (100 mg/kg) of USKECSE to adult rats, kaempferol was detectable for 48 hours, suggesting its significant absorption and distribution in plasma. Peak kaempferol concentration in plasma (C max ) was 483 ng/ml (2 μM), and at this concentration, kaempferol induces osteoblast differentiation. USKECSE had no genotoxicity, and its safety index assessed by preclinical toxicity studies, including safety pharmacology, was >20-fold. Taken together, we report a novel extraction process that enhanced the osteogenicity and concomitantly reduced hepatotoxicity of tea extract with significant kaempferol bioavailability and a favorable systemic safety profile. Based on these data, we propose assessing the USKECSE effect for postmenopausal osteoporosis treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kulkarni, Sharma, Bora, Verma, Rajput, Porwal, Rath, Gayen, Sharma and Chattopadhyay.)