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Purpose: This study aims to establish DROL (disruption of retinal outer layers), PROS (photoreceptor outer segment length), SND (subfoveal neuroretinal detachment), and hyperreflective walls of foveal cystoid spaces (HRW) as optical coherence tomography (OCT) biomarkers and predictors of central macular thickness (CMT) and visual acuity in diabetic macular edema (DME) treated with intravitreal ranibizumab (IVR). Methods: In this prospective, interventional study performed at a tertiary care center over a span of 1 year from December 2021 to December 2022, 50 eyes of 46 patients of DME were included. Visual acuity and spectral domain OCT imaging were performed at baseline. Using inbuilt calipers on SD-OCT, the horizontal extent of DROL and the vertical extent of PROS were measured manually. SND and HRW were assessed qualitatively. IVR was administered and patients were followed up at 4, 8, and 12 weeks. Results: The eyes without DROL had statistically significant (P < 0.05) lesser CMT and better BCVA (best-corrected visual acuity) (P < 0.05) after pro re nata injection of IVR. There was a positive correlation between the extent of baseline DROL with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05), whereas negative correlation with the extent of baseline PROS with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05). The presence of HRW and SND predicted non-resolution of CMT and worse visual acuity after treatment with IVR in DME . Conclusion: DROL, PROS, SND, and hyperreflective walls of foveal cystoid spaces may be utilized as qualitative as well as quantitative biomarkers to predict the post-treatment CMT and visual acuity in DME. Keywords: Diabetic macular edema (DME), disruption of retinal outer layers (DROL), ellipsoid zone (EZ), hyperreflective walls of foveal cystoid spaces, interdigitation zone (IZ), photoreceptor outer segment length (PROS), subfoveal neuroretinal detachment (SND), Author(s): Ayushi Sardana (corresponding author) [1]; Kamaljeet Singh [1]; Arti Singh [1]; Vinod K Singh [1] Diabetes is a chronic, metabolic disease that occurs either when the pancreas does not [...]

Byline: Vineet. Yadav, Jagriti. Rana, Arti. Singh, Kamal. Singh, Santosh. Kumar, Shivangi. Singh Purpose: Evaluation of ganglion cell-inner plexiform layer thickness in the diagnosis of pre-perimetric glaucoma (PPG) and comparison [...]

Byline: Arti. Singh, Kamaljeet. Singh, Jagriti. Rana, Upasna. Singh, Anirrud. Sharma, Vineet. Kumar Hyaluronidase is an often used drug in ophthalmology to enhance the effect of local anesthesia. Hypersensitivity reaction [...]

Graphical abstract:

AIIRAseeks to transform agriculture by creating a new AI‐driven framework for modeling plants at various agronomically relevant scales. We accomplish this by designing and deploying AI‐driven predictive models that fuse diverse data with siloed domain knowledge. AIIRA's vision, illustrated in Figure 1, consists of four technical thrusts with cross‐cutting education, training, and outreach activities. Our activities are focused on theory, algorithms, and tools for the principled creation of goal‐oriented AI tools deployed at plant and field scales. Our use‐inspired AI developments are tightly integrated with USDA‐relevant challenges in crop improvement and sustainable crop production. Our strong social science focus ensures sustained AI adoption across the ag value chain. Our cyberinfrastructure (CI) efforts ensure cohesive, sustainable, and extensible CI to reproducibly share and manage data assets and analysis workflows to a diverse spectrum of the Ag community. Taken together, this will ensure long‐term payoffs in AI and agriculture. AIIRAhas established a new field of Cyber Agricultural Systemsat the intersection of plant science, agronomics, and AI. Our signature activities build the workforce for this new field through formal and informal educational activities. Through these activities, AIIRAcreates accessible pathways for underrepresented groups, especially Native Americans and women.

Neurodegenerative diseases are a group of pathological conditions that cause motor incordination (jerking movements), cognitive and memory impairments result from degeneration of neurons in a specific area of the brain. Oxidative stress, mitochondrial dysfunction, excitotoxicity, neuroinflammation, neurochemical imbalance and histone deacetylase enzymes (HDAC) are known to play a crucial role in neurodegeneration. HDAC is classified into four categories (class I, II, III and class IV) depending upon their location and functions. HDAC1 and 2 are involved in neurodegeneration, while HDAC3-11 and class III HDACs are beneficial as neuroprotective. HDACs are localized in different parts of the brain- HDAC1 (hippocampus and cortex), HDAC2 (nucleus), HDAC3, 4, 5, 7 and 9 (nucleus and cytoplasm), HDAC6 & HDAC7 (cytoplasm) and HDAC11 (Nucleus, cornus ammonis 1 and spinal cord). In pathological conditions, HDAC up-regulates glutamate, phosphorylation of tau, and glial fibrillary acidic proteins while down-regulating BDNF, Heat shock protein 70 and Gelsolin. Class III HDACs are divided into seven sub-classes (SIRT1-SIRT7). Sirtuins are localized in the different parts of the brain and neuron -Sirt1 (nucleus), Sirt2 (cortex, striatum, hippocampus and spinal cord), Sirt3 (mitochondria and cytoplasm), Sirt4, Sirt5 & Sirt6 (mitochondria), Sirt7 (nucleus) and Sirt8 (nucleolus). SIRTs (1, 3, 4, and 6) are involved in neuronal survival, proliferation and modulating stress response, and SIRT2 is associated with Parkinsonism, Huntington’s disease and Alzheimer’s disease, whereas SIRT6 is only associated with Alzheimer’s disease. In this critical review, we have discussed the mechanisms and therapeutic targets of HDACs that would be beneficial for the management of neurodegenerative disorders

High‐throughput phenotyping (HTP) with unoccupied aerial systems (UAS), consisting of unoccupied aerial vehicles (UAV; or drones) and sensor(s), is an increasingly promising tool for plant breeders and researchers. Enthusiasm and opportunities from this technology for plant breeding are similar to the emergence of genomic tools ∼30 years ago, and genomic selection more recently. Unlike genomic tools, HTP provides a variety of strategies in implementation and utilization that generate big data on the dynamic nature of plant growth formed by temporal interactions between growth and environment. This review lays out strategies deployed across four major staple crop species: cotton (Gossypium hirsutumL.), maize (Zea maysL.), soybean (Glycine maxL.), and wheat (Triticum aestivumL.). Each crop highlighted in this review demonstrates how UAS‐collected data are employed to automate and improve estimation or prediction of objective phenotypic traits. Each crop section includes four major topics: (a) phenotyping of routine traits, (b) phenotyping of previously infeasible traits, (c) sample cases of UAS application in breeding, and (d) implementation of phenotypic and phenomic prediction and selection. While phenotyping of routine agronomic and productivity traits brings advantages in time and resource optimization, the most potentially beneficial application of UAS data is in collecting traits that were previously difficult or impossible to quantify, improving selection efficiency of important phenotypes. In brief, UAS sensor technology can be used for measuring abiotic stress, biotic stress, crop growth and development, as well as productivity. These applications and the potential implementation of machine learning strategies allow for improved prediction, selection, and efficiency within breeding programs, making UAS HTP a potentially indispensable asset. UAS imagery can be useful in plant breeding programs for routine trait and previously infeasible trait measurement.High‐throughput phenotyping approaches to date differ among crops and each could learn from others.Example applications of UAS imagery are provided for breeding programs of four major crops.The rise of phenomics tools is likely to prove similarly useful to current genomic tools.

Background:The fields of stroke genomics, biobanking, and precision medicine are rapidly expanding in sub-Saharan Africa. However, the ethical, legal, and social implications (ELSI) of emerging neurobiobanking and genomic data resources are unclear in an emerging African scientific landscape with unique cultural, linguistic, and belief systems.Objective:This article documents capacity-building experiences of researchers during the development, pretesting, and validation of data collection instruments of the African Neurobiobank for Precision Stroke Medicine—(ELSI) Project.Methods:The African Neurobiobank for Precision Stroke Medicine—ELSI project is a transnational, multicenter project implemented across seven sites in Ghana and Nigeria. Guided by the Community-Based Participatory Research framework, we conducted three workshops with key stakeholders to review the study protocol, ensure uniformity in implementation; pretest, harmonize, and integrate context-specific feedback to ensure validity and adaptability of data collection instruments. Workshop impact was assessed using an open-ended questionnaire, which included questions on experience with participation in any of the workshops, building capacity in Genetic and Genomic Research (GGR), level of preparedness toward GGR, the genomic mini-dictionary developed by the team, and its impact in enhancing understanding in GGR. Data were analyzed qualitatively using a thematic framework approach.Results:Findings revealed the usefulness of the workshop in improving participants' knowledge and capacity toward GGR implementation. It further identified local, context-specific concerns regarding quality data collection, the need to develop culturally acceptable, genomic/biobanking data collection tools, and a mini-dictionary. Participants-reported perceptions were that the mini-dictionary enhanced understanding, participation, and data collection in GGR. Overall, participants reported increased preparedness and interest in participating in GGR.Conclusion:Capacity-building is a necessary step toward ELSI-related genomic research implementation in African countries where scholarship of ELSI of genomics research is emerging. Our findings may be useful to the design and implementation of ELSI-GGR projects in other African countries.

The endophytic fungi are the endosymbiont which play important role in improving host plant fitness and source of plethora of bioactive molecules. Present study includes the assessment of antimicrobial activity, phytochemical analysis and enzymes activity of fungal endophyte EHL2, isolated from leaf tissues of an Indian medicinal plant Euphorbia hirtaL. The fungus exhibited the antibacterial and antifungal activities against a broad range of bacterial and fungal pathogens. To the best of our knowledge, this is the first report about the isolation and characterization of endophytic fungus Nigrospora sphaerica(EHL2) recovered from E. hirtaL. The minimum inhibitory concentration (MIC) of the crude extract against pathogenic bacteria ranged from 0.45 to 3.14 mg/ml. For antifungal ativity of fungus, the highest percentage of inhibition was observed against Colletotrichumsp. (33.78%) while, minimum activity was noticed against Alternaria solani(16.60%).Preliminary mycochemical analysis revealed the positive tests for alkaloids, phenolics, flavonoids and terpenoids. The results showed that the total phenolic content (TPC) and total flavonoid content (TFC) of crude extracts were 78.11 ± 0.04 mg GAE/g and 235.94 ± 3.06 mg RE/g, respectively.Furthermore, the fungus also produced amylase, cellulase, protease and laccase enzymes. In conclusion, these positive results of mycochemicals and enzymes activity displayed by N. sphaericaof E. hirtaprovide an opportunity which could be exploited for host protection against pathogens and enzyme production.

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ABSTRACTStroke is a major cause of death in Sub-Saharan Africa (SSA) and genetic factors appear to play a part. This led to the development of stroke bio-banking and genomics research in SSA. Existing stroke studies have focused on causes, incidence rates, fatalities and effects. However, scant attention has been paid to the legal issues about stroke bio-banking and genomics research in the sub-region. Therefore, this article examines how genomics research and stroke bio-banking in SSA can be regulated through legislation. The article reports that there are germane issues to be addressed such as appropriate consent model, commercial use of biological samples, ownership right in biological samples and return of research results but that the position of the law on these issues is not satisfactory because there is no statute directly regulating them while existing regulations in these countries are either absent, outdated, conservative or difficult to navigate. The article, therefore, applies the theory of symbolic legislation and argues for legislative intervention through a positive symbolic approach. It recommends that the statute to be enacted should only address policy issues by way of legal rules without being detailed while the understanding of the rules should be fostered in explanatory notes. The explanatory notes should contain examples borne of decided cases, cases settled out of court and the ethical guidelines prepared by Human Heredity and Health in Africa (H3 Africa). Where they are inadequate, recourse may be had to other ethical guidelines subject to the demands of local circumstances.

Global and midwestern U.S. agriculture requires diversification and new sources of protein for sustainable crop production. Mung bean [Vigna radiata(L.) R. Wilczek] as a legume crop has a long cultivation history in Asia; however, its potential lays hitherto underexplored in the United States. As a first step towards exploring mung bean for crop diversification in northern latitudes, crop germplasm centers that harbor worldwide crop resources need to be used. This study explores the potential of mung bean in the U.S. northern latitudes through the utilization of the USDA germplasm resources. Complete collection of USDA mung bean germplasm was screened under Iowa field conditions in 2017, to shortlist 482 accessions to create an Iowa mung bean panel. The Iowa mung bean panel was further characterized for field adaptability traits in 2018 and 2019 and genotyped using genotype‐by‐sequencing (GBS) to conduct association mapping of important traits. Genetic markers were identified for both quantitative trait (days to flowering [DTF], plant height [PHT], leaf drop at maturity [LDMS], 100‐seed weight [SDWT], and Fusarium wilt score [WS]) and qualitative traits (seed color [SC], seed‐coat texture [ST], hypocotyl color [HC], and pod color [PC]). We report FERONIA, a known flowering‐pathway gene, as the candidate gene for the quantitative trait locus (QTL) with largest effect on DTF. In addition, important epistatic interactions were also uncovered for WS and SDWT. Further, accessions with desirable magnitude of traits were identified as potential parents. Diversity analyses and field phenotypic data indicate potential for mung bean improvement to suit midwestern U.S. cultivation.

AbstractAntibiotic resistance is a global threat whose incidences are increasing day by day worldwide. Thus, there is a need for new chemical entities (NCEs) or exploration of existing molecules against these types of infections. In the current investigation, we have tested the inhibitory potential of four different phytomolecules (berberine, gallic acid, piperine, and rutin) against bacterial biofilm and efflux pumps by using in-silicoand in-vitrotechniques. The phytomolecules (berberine, piperine, and rutin) except gallic acid have shown good interaction towards biofilm and efflux pump proteins. Further, In-vitrostudies have also shown the good inhibitory effect of tested phytomolecules (berberine, rutin, and piperine) against bacterial biofilm formation and efflux pumps. In conclusion, berberine, piperine, and rutin could be the promising antibacterial candidates, particularly against resistant bacterial strains.Communicated by Ramaswamy H. Sarma

Background: Infections are one of the leading causes of death worldwide and currently available treatments remain unsatisfactory due to rise in the cases of antimicrobial resistance. Thus, there is a need for the development of new drugs with different mechanisms of action. However, the development of new antimicrobials agents is a long and expensive process. Hence, most of the pharmaceutical companies are looking forward to repurposing the already available drugs against microbial infections. Methodology: The data related to SERMs and microbial infection has been extracted from Pub Med (from January 1997 to December 2018). A total of 101 studies have been published from 1997 -2018 regarding SERMs and microbial infections. Results: On the basis of inclusion and exclusion criteria, 25 studies have been included for the analysis of level of evidence regarding antimicrobial effects of SERMs. Emerging reports have indicated the antimicrobial property of selective estrogen receptor modulators (SERMs) against normal and resistant strains under in vitro and in vivo conditions against wide variety of microorganisms through different mechanisms of action. Conclusion: In conclusion, SERMs could be developed as a broad spectrum antimicrobial agent alone or in combination with existing antimicrobial agents.

Background and Significance:

Neuropathic Pain (NP) is a painful condition which is a direct consequence of a lesion or disease affecting the somatosensory system with symptoms like allodynia, hyperalgesia. It has complex pathogenesis as it involves several molecular signaling pathways, thus numerous reliable animal models are crucial to understand the underlying mechanism of NP and formulate effective management therapy. Some models like spinal cord injury, chronic constriction injury, spinal nerve ligation, chemotherapy induced peripheral neuropathy, diabetes-induced NP and many more are discussed. This review contains an overview of the procedures followed to induce neuropathy and specific characteristics of that particular model. Some new techniques like spared nerve ligation, have omitted the limitation of methods not presently used where complete nerve damage occurs. Since animal models provide a window to experienced symptoms and physiology and impact the translation of bench discoveries to the bedside, the reporting, interpretation and comparison of these models is necessary because slight variation in procedure of model generation can drastically alter the results. The development of novel, but rational analgesic drugs to alleviate this intractable pain demands elucidation of molecular mechanisms of NP for which different types of animal models have been established.

There has been a tremendous surge in stroke prevalence in sub-Saharan Africa. Hypertension (HTN), the most potent, modifiable risk factor for stroke, is a particular challenge in sub-Saharan Africa. Culturally sensitive, efficacious HTN control programs that are timely and sustainable are needed, especially among stroke survivors. Mobile health (mHealth) technology and task-shifting offer promising approaches to address this need.

ABSTRACTIntroduction:Role of Glutathione-S-transferases (GSTs) has been well explored in the cellular detoxification process, regulation of redox homeostasis and S-glutothionylation of target proteins like JNK, ASK1 etc. However, altered levels or functions of this enzyme or their subtypes have emerged in the development of several pathologies diseases such as Alzheimer’s disease, Parkinson’s disease, cancer and related conditions. Oxidative stress is one of the possible pathological events that contributes significantly to activation of degenerating cascades inside neuronal cells. The central nervous system is highly sensitive to oxidative stress because of low levels or capacities of antioxidant enzymes. The brain is highly metabolic in nature making it susceptible to oxidative stress.Areas covered:The present review provides a comprehensive overview of the multiple connections of GSTs within diverse neurological diseases including cancer. Furthermore, the authors have made significant efforts to discuss the regulation of different GST isoforms that have been associated with various pathological processes such as glioblastoma, Alzheimer’s disease, Parkinson’s disease, stroke and epilepsy.Expert opinion:Though GSTs have been one of the key areas of scientific research over the last few decades, much remains to be elucidated about their physiological functions as well as pathological involvement of GSTs and their polymorphic variants.

In this paper, a credit risk optimisation model for the portfolio of credit risky bonds with l∞-norm risk measure is proposed. The proposed model is formulated as a linear programming problem which makes it computationally efficient for the portfolio of large size. The rates of returns of the bonds are the input parameters of the proposed model and of the other portfolio optimisation models which are considered for the comparison with the former. The complete approach of generating rate of returns of the bonds, given their initial credit ratings and transition probability matrices, is presented. The time homogeneous discrete time Markov chain model is assumed for the credit rating dynamics of bonds. With extensive numerical illustrations, the proposed approach of obtaining rate of returns of the bonds is demonstrated. Furthermore, comparison of the proposed credit risk optimisation model with other inline existing portfolio optimisation models is performed.

Microwave irradiation technology has a lot of applications in the field of food processing, organic synthesis, pharmaceuticals, and biomedical therapy. The basic mechanisms observed in microwave-assisted syntheses are dipolar polarization and conduction. Of late, it has gained tremendous attention in the synthesis of drug delivery systems for enhanced solubility, dissolution rate, and biopharmaceutical attributes. Considering the myriads of advantages over conventional heating such as high percentage yield, lesser reaction time, deep penetration of heat, and improved product quality; microwave-assisted technology holds potential in the development of nano- and microparticle-based drug delivery systems with improved physicochemical characteristics and thereby, bioavailability. In this review, we have discussed the formulation of drug delivery systems which includes lipidic, polymeric, metallic, and micellar nanoparticles. We have also summarized solid dispersion, dendrimers, and carbon nanotubes in this manuscript. However, it is possible to expedite the extraction process, save expenses, and increase the effectiveness, reliability, and simplicity of responses. Therefore, microwave technology provides a new avenue for the development of drug delivery systems in various biomedical applications.

•Tax and price measures have been proposed as tobacco control tools.•Ghana's first study on cigarette prices and aggregate cigarette consumption.•Cigarette demand is significantly influenced by prices.•Tobacco taxation will reduce cigarette consumption.

Alzheimer's disease (AD), a common neurodegenerative disorder, recognized to be a major cause of dementia. The aim of the present study was to investigate the neuroprotective mechanisms of clove oil in intracerebroventricular (icv)-colchicine induced cognitive dysfunction in rats.

The aim of the present work is to develop rifampicin loaded phospholipid lipospheres containing sulfphobutyl ether β-cyclodextrin and Vitamin C for inhalation to test their potential for deep lung delivery. The findings of the solid state characterization revealed the amorphous nature of the lipospheres. These exhibited a better flowability, an aerodynamic diameter in the range of 1.76 to 3.99 µm. Moreover, the fine particle fraction and emitted dose was found in the range of 68.84–83.73% and 80–93%, respectively. Moreover, lipospheres exhibited enhanced/equivalent efficacy in vitroin H37Rv strain. Hence, the results show the potential of lipospheres for pulmonary delivery of rifampicin.

The human body is made up of various external skin barriers to fight disease and infection. One such barrier is mucus, which not only protects and lubricates the exposed epithelia by preventing entry of pathogens, unwanted particles, and debris, but also prevents diffusion of mucosal drug delivery. In recent decades, mucoadhesion has received much attention for various drug delivery systems that involve the interaction between the dosage form and the mucosal surface. Transmucosal administration has become challenging due to various factors affecting the mucus barrier properties, mainly particle size, thickness, interaction of the particles with the mucosa, clearance time and rate. This review article describes the role, composition, and physicochemical properties of a mucus that affects penetration and aims to provide scientists with a roadmap to conduct high-quality research for the design and development of mucoadhesive delivery systems such as buccal, nasal, gastrointestinal, pulmonary, and vaginal through surface modification to avoid rapid clearance, ensure targeted and sustained drug delivery, improve residence time and the overall therapeutic efficacy of a drug, along with easy permeation of particles through the mucosal surface for efficient treatment of diseases with fewer side effects.

Approximately 40% and 90% of the drugs developed and in the developing phase, suffer from poor aqueous solubility, and thereby exhibiting declined oral bioavailability and restricted enteric permeability. Phenolic compounds comprise a collection of phytochemicals, possessing low water solubility, thus limiting their clinical applications. This makes them a classical contender for thorough analysis and application in formulation development. It exhibits several useful pharmacological activities including anti-inflammatory, antioxidant, anticancer, and neuroprotective. Even though preclinical, clinical, and FDA approval describe the advantages and credibility of trans-ferulic acid; its medicinal applicability as a therapeutic compound is finite owing to low solubility and bioavailability. Nanotechnology-based formulation development scheme is generally applied to overcome biopharmaceutical drawbacks of hydrophobic drugs. The principal objective of this manuscript is to present a review of conventional and novel synthesis mechanisms, structural activity relationship, physicochemical properties, and anticancer impacts of ferulic acid. Finally, we have reviewed various emerging and advanced formulations of ferulic acid. We hope that this review would offer an opportunity for formulation scientists to bridge the preclinical and clinical gaps.

Alzheimer's disease acknowledged as progressive multifarious neurodegenerative disorder, is the leading cause of dementia in late adult life. Pathologically it is characterized by intracellular neurofibrillary tangles and extracellular amyloidal protein deposits contributing to senile plaques. Over the last two decades, advances in the field of pathogenesis have inspired the researchers for the investigation of novel pharmacological therapeutics centered more towards the pathophysiological events of the disease. Currently available treatments i.e. acetylcholinesterase inhibitors (rivastigmine, galantamine, donepezil) and N-methyl d-aspartate receptor antagonist (memantine) contribute minimal impact on the disease and target late aspects of the disease. These drugs decelerate the progression of the disease, provide symptomatic relief but fail to achieve a definite cure. While the neuropathological features of Alzheimer's disease are recognized but the intricacies of the mechanism have not been clearly defined. This lack of understanding regarding the pathogenic process may be the likely reason for the non-availability of effective treatment which can prevent onset and progression of the disease. Owing to the important progress in the field of pathophysiology in the last couple of years, new therapeutic targets are available that should render the underlying disease process to be tackled directly. In this review, authors will discusses the different aspects of pathophysiological mechanisms behind Alzheimer's disease and its management through conventional drug therapy, including modern investigational therapeutic strategies, recently completed and ongoing.

Tuberculosis (TB) has been the most life-threatening contagious disease caused by pathogenic mycobacterium tuberculosis.The World Health Organization (WHO) report, 2020 estimated that this highly burden bacterial infection becomes the prime root for the death of 1.4 million people worldwide. There are several conventional regimens have been approved to treat this disease. However, due to long term therapy, liver toxicity, multiple dosing frequency and multi- and extensive drug resistance leads to patient non-complaint. Moreover, the complex nature of mycobacterial cells, granuloma formation, high dose, and alteration of gene expression also stand as a barrier that limits the use of conventional treatment. Hence, to mitigate quality life-infected controversial pathways, nanotechnology-based novel nanocarriers are emerging as a bloom strength to cure the deadliest tuberculosis. The current situation is aggressively been engaged in exploring novel nanomedicines that ultimately overcome the drawback associated with traditional tuberculosis treatment. Therefore, this review summarizes recent advancements in the nanomedicine-based delivery system for the treatment of pulmonary tuberculosis. We have explored current ongoing research such as polymeric, lipidic, metallic, phytofabricated, ligand anchored, nanoembedded microparticles, and multifunctionalized nanoparticles. In addition, this review also discusses challenges of nanomedicines in terms of toxicological and clinical aspects in terms of scale-up method, optimization of formualtion for clinical studies and quantification of drug in the humans are also discussed. We believe that this review will provide an insight on the role of nanomedicines in the treatment of pulmonary tuberculosis.

Several studies have stated that mucus is a critical hurdle for drug delivery to the mucosal tissues. As a result, Polymeric nanoparticles that can overcome mucus barriers are gaining popularity for controlled drug delivery into intra-macrophages to attain high intracellular drug concentration. The present study was aimed to fabricate inhalable N-acetylcysteine (NAC) modified PLGA mucus penetrating particles using the double emulsion method (w/o/w) for target delivery to alveolar macrophages and minimize the dose-related adverse effects, efficiently encapsulate hydrophilic drug, sustain the release profile and prolong the retention time for the management of tuberculosis. Among the numerous formulations, the drug/polymer ratio of 1:10 with 0.50% PVA concentration and sonication time for 2 ​min ​s was chosen for further research. The formulated nanoparticles had a mean particle size of 307.50 ​± ​9.54 ​nm, PDI was 0.136 ​± ​0.02, zeta potential about −11.3 ​± ​0.4 ​mV, decent entrapment efficiency (55.46 ​± ​2.40%), drug loading (9.05 ​± ​0.22%), and excellent flowability. FTIR confirmed that NAC and PLGA were compatible with each other. SEM graphs elucidated that the nanoparticles were spherically shaped with a slightly rough surface whereas TEM analysis ensured the nanometer size nanoparticles and coating of lipid over NPs surface. PXRD spectrum concluded the transformation of the drug from crystalline to amorphous state in the formulation. In vitrorelease pattern was biphasic started with burst release (64.67 ​± ​1.53% within 12hrs) followed by sustained release over 48hrs thus enabling the prolonged replenishing of NAC. In vitrolung deposition study pronounced that coated NAC-PLGA-MPPs showed favorable results in terms of emitted dose (86.67 ​± ​2.52%), MMAD value (2.57 ​± ​0.12 ​μm), GSD value (1.55 ​± ​0.11 ​μm), and FPF of 62.67 ​± ​2.08% for the deposition and targeting the lungs. Finally, in vitroefficacy studies demonstrated that NAC-PLGA-MPPs presented more prominent antibacterial activity against MTBH37Rv strain as compared to NAC. Hence, PLGA based particles could be a better strategy to deliver the NAC for lung targeting.

Numerous oral treatment options have been reported for neurological diseases, particularly Alzheimer's disease (AD). Berberine (BRB), a promising phytoactive drug, has been successfully explored for effective therapeutic management of AD and other neurodegenerative disorders. However, it poses formidable challenges of exceedingly poor oral bioavailability of 0.68%, primarily owing to its poor intestinal permeation, extremely low aqueous solubility, and extensive P-glycoprotein efflux transport. The present studies, accordingly, were undertaken to develop the galactose-tethered nanostructured lipidic carriers of BRB for efficient brain uptake. NLCs were systematically developed and optimized using QbD paradigms, and thoroughly characterized for particle size, zeta potential, morphology, entrapment efficiency and in vitrodrug release. U-87 cell lines studies indicated augmentation in cellular permeability and uptake of the galactosylated NLCs. Oral bioavailability was found to be highly significantly enhanced with over 8.21-folds and 3.56-folds (p < 0.001 each) improvement in the values of AUC48hand Cmax, respectively, along with substantial elevation in brain drug levels too (p < 0.05 to p < 0.001). Also, tmaxwas found to be notably increased by 1.41-folds (p < 0.05), indicating extended release characteristics of the galactosylated NLCs. Studies on brain homogenates exhibiting distinctly superior biochemical parameters, and behavioural studies demonstrating marked cognitive potential in β-amyloid treated rats further substantiated their promising utility in the management of AD. High degree of Level A linear correlations were established between fractions of drug dissolved (in vitro) and of drug absorbed (in vivo) BRB and its NLC formulations. Stability studies at 5 °C indicated robustness of galactosylated NLCs for 6 months. The current preclinical findings, accordingly, offer distinctive potential of the developed NLCs in enhanced drug efficacy, extended duration of action and effective therapeutic management of AD.

Chemotherapy is an important component of cancer treatment, which has side effects like vomiting, peripheral neuropathy, and numerous organ toxicity but the most significant outcomes of chemotherapy are cognitive impairment, which is mainly referred to as chemobrain or CICI (chemotherapy-induced cognitive impairment). It is characterized by difficulty with language, concentrating, processing speed, learning, and memory, as it affects the hippocampus areas of the brain. Mitochondrial dysfunction and oxidative stress are one of the major mechanisms causing chemobrain. The generation of reactive oxygen species (byproducts of oxidative phosphorylation) mainly occurs in mitochondria that play a prominent role in the induction of oxidative stress. The homeostasis of ROS in the mitochondria is maintained by mitochondrial antioxidant mechanism via enzymes like catalase, glutathione, and superoxide dismutase. Lungs and breast cancer are the two most common types of cancer, which are the most leading cancers in the world with about 4.18 million cases. In this review we exposed the current knowledge regarding chemotherapy-induced oxidative stress and mitochondrial dysfunction to cause cognitive impairment.We especially focused on the antineoplastic agent (ADRIAMYCIN, CYCLOPHOSPHAMIDE), platinum group agent CISPLATIN, antimetabolite agents (METHOTREXATE), and nitrogen mustard agent (CARMUSTINE) which increase oxidative stress and inflammatory markers in the PNS (peripheral nervous system) as well as the central nervous system. We also highlight the behavioural and functional changes in the brain.

Aim:This study was conducted to explore the antibacterial potential of selective estrogen receptor modulators (SERMs). Materials & methods:The percentage growth retardation, bacterial growth kinetics, biofilm, checkerboard and bacterial burden assays were conducted to check antibacterial potential of SERMs. Finally, docking study was also conducted to predict possible antibacterial mechanism of SERMs. Results:In vitroand in vivostudies have shown the antibacterial activity of SERMs against different tested strains of bacteria. The synergistic activity of SERMs in combination with standard antibacterial agents was also observed and tested further under in vivoconditions. In vivoresults have shown decreased bacterial bioburden. Docking studies have predicted the multimodal antibacterial mechanism of SERMs. Conclusion:SERMs can be considered as promising broad-spectrum antibacterial agents.