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Photodynamic therapy (PDT), as the name suggests is a light-based, non-invasive therapeutic treatment method that has garnered immense interest in the recent past for its efficacy in treating several pathological conditions. PDT has prominent use in the treatment of several dermatological conditions, which consequently have cosmetic benefits associated with it as PDT improves the overall appearance of the affected area. PDT is commonly used for repairing sun-damaged skin, providing skin rejuvenation, curbing pre-cancerous cells, treating conditions like acne, keratosis, skin-microbial infections, and cutaneous warts, etc. PDT mediates its action by generating oxygen species that are involved in bringing about immunomodulation, suppression of microbial load, wound-healing, lightening of scarring, etc. Although there are several challenges associated with PDT, the prominent ones being pain, erythema, insufficient delivery of the photosensitizing agent, and poor clinical outcomes, still PDT stands to be a promising approach with continuous efforts towards maximizing clinical efficacy while being cautious of the side effects and working towards lessening them. This article discusses the major skin-related conditions which can be treated or managed by employing PDT as a better or comparable alternative to conventional treatment approaches such that it also brings about aesthetic improvements thereof.

Cancer is one of the major causes of mortality, accounting for ∼ 9.5 million deaths globally in 2018. The spectrum of conventional treatment for cancer includes surgery, chemotherapy and radiotherapy. Recently, cold plasma therapy surfaced as a novel technique in the treatment of cancer. The FDA approval of the first trial for the use of cold atmospheric plasma (CAP) in cancer therapy in 2019 is evidence of this. This review highlights the mechanisms of action of CAP. Additionally, its applications in anticancer therapy have been reviewed. In summary, this article will introduce the readers to the exciting field of plasma oncology and help them understand the current status and prospects of plasma oncology.

Abstract: Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disorder, manifested by the loss of memory and cognitive abilities, behavioral disturbance and progressive impairment of activities of daily life. The sharp rise in the number of AD patients has brought it with-in the top eight health issues in the world. It is associated with the distribution of misfolded aggre-gates of protein within the brain. However, Alois Alzheimer initially mentioned that the reduction in brain volume in AD might be associated with the “deposition of a special substance in the cortex”. The resulting plaque found in extracellular space in the AD brain and hippocampus region, known as senile plaques, is the characteristic feature underlying Alzheimer’s pathology, where the role of amy-loid-β (Aβ) peptide formation from proteolytic cleavage of amyloid precursor protein (APP) by secre-tase enzyme is eminent. Therefore, this review has highlighted the molecular pathophysiology of AD with a variety of available diagnostic and treatment strategies for the management of the disease, with a focus on the advancement toward clinical research to provide new effective and safe tool in the diagnosis, treatment or management of AD.

Purpose A literature review revealed that government of various developing economies have put an effort on health-care supply chain through the executing critical factors (CFs) directly. Although they have attained some significant benefits in this tactic, but it was not up to satisfactory level. One of the reasons can be attributed to the fact that government/policy makers are not quantifying the impact of CFs on health-care supply chain. This paper aims to propose a methodology to quantify and estimate the impact of CFs on government-supported health-care supply chain (GHSC). Design/methodology/approach The Graph Theoretic Approach is proposed for estimating the impact and utility of CFs on an Indian GHSC. This study is also extended to scenario analysis for comparing results with different performance situation. Findings The results obtained from this study show that performance of Indian GHSC is satisfactory, but performance gaps exist which need to be reduced. In this research work, 12 CFs are identified under two significant categories (SCs), i.e. enablers and barriers and the intensity of enablers and barriers have been calculated to show the impact or influence of CFs on GHSC. The value of intensity shows that the role or impact of enabler category (i.e. performance measurement, employee recognition and reward, technology adoption, training cell, inbuilt analytical tool for IT system) is higher on Indian GHSC in comparison to barriers category to enhance the performance of GHSC. Research limitations/implications The obtained numerical results are completely in specific to the Indian perspective only; hence, they cannot be generalized for other countries. Simultaneously, this study is related to government supported health-care system; hence, the selection of expert panel was crucial due to the unavailability of doctors and other stakeholders of government system. Practical implications The proposed approach is aimed at providing a procedure for evaluating the impact of CFs on HSC in general and GHSC in specific. This study is an attempt to assist government and top management of GHSC to assess the impact of CFs on GHSC and accordingly define its course of actions. Originality/value Although various issues related to the CFs have been broadly identified and analyzed, no dedicated study has been reported in the field for quantification of impacts of CFs. Furthermore, this proposed model has an ability to recognize the specific contribution of each CF and overall contribution.

Alzheimer type of dementia is accompanied with progressive loss of cognitive function that directly correlates with accumulation of amyloid beta plaques. It is known that Fibroblast growth factor 21 (FGF21), a metabolic hormone, with strong neuroprotective potential, is induced during oxidative stress in Alzheimer's disease. Interestingly, FGF21 cross-talks with autophagy, a mechanism involved in the clearance of abnormal protein aggregate. Moreover, autophagy activation by Rapamycin delivers neuroprotective role in Alzheimer's disease. However, the synergistic neuroprotective efficacy of overexpressed FGF21 along with Rapamycin is not yet investigated. Therefore, the present study examined whether overexpressed FGF21 along with autophagy activation ameliorated neurodegenerative pathology in Alzheimer's disease. We found that cognitive deficits in rats with intracerebroventricular injection of Amyloid beta

Cold atmospheric plasma therapy is a new and latest approach whose arrival has astonished experts all around the world from the area of biological and pharmaceutical sciences. Owing to its simple and non-invasive nature, this technique has been admired and encouraged to use different therapeutic regimes like wound healing, ulceration, and cancer. It is often confused with blood plasma but is identified as the fourth state of matter generated using feed gases like atmospheric air, argon, helium either by applying irradiation or electric field. The non-thermal property of plasma (cold plasma) is mainly focused on the clinical application as it utilizes lower temperatures (

Brain, a subtle organ of multifarious nature presents plethora of physiological, metabolic and bio-chemical convolutions that impede the delivery of biomolecules and thereby resulting in truncated therapeutic outcome in pathological conditions of central nervous system (CNS). The absolute bottleneck in the therapeutic management of such devastating CNS ailments is the BBB. Another pitfall is the lack of efficient technological platforms (due to high cost and low approval rates) as well as limited clinical trials (due to failures of neuro‑leads in late-stage pipelines) for CNS disorders which has become a literal brain drain with poorest success rates compared to other therapeutic areas, owing to time consuming processes, tremendous convolutions and conceivable adverse effects. With the advent of intranasal delivery (via direct N2B or indirect nose to blood to brain), several novel drug delivery carriers viz. unmodified or surface modified nanoparticle based carriers, lipid based colloidal nanocarriers and drysolid/liquid/semisolid nanoformulations or delivery platforms have been designed as a means to deliver therapeutic agents (small and large molecules, peptides and proteins, genes) to brain, bypassing BBB for disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, schizophrenia and CNS malignancies primarily glioblastomas. Intranasal application offers drug delivery through both direct and indirect pathways for the peripherally administered psychopharmacological agents to CNS. This route could also be exploited for the repurposing of conventional drugs for new therapeutic uses. The limited clinical translation of intranasal formulations has been primarily due to existence of barriers of mucociliary clearance in the nasal cavity, enzyme degradation and low permeability of the nasal epithelium. The present review literature aims to decipher the new paradigms of nano therapeutic systems employed for specific N2B drug delivery of CNS drugs through in silico complexation studies using rationally chosen mucoadhesive polymers (exhibiting unique physicochemical properties of nanocarrier's i.e. surface modification, prolonging retention time in the nasal cavity, improving penetration ability, and promoting brain specific delivery with biorecognitive ligands) via molecular docking simulations. Further, the review intends to delineate the feats and fallacies associated with N2B delivery approaches by understanding the physiological/anatomical considerations via decoding the intranasal drug delivery pathways or critical factors such as rationale and mechanism of excipients, affecting the permeability of CNS drugs through nasal mucosa as well as better efficacy in terms of brain targeting, brain bioavailability and time to reach the brain. Additionally, extensive emphasis has also been laid on the innovative formulations under preclinical investigation along with their assessment by means of in vitro /ex vivo/in vivo N2B models and current characterization techniques predisposing an efficient intranasal delivery of therapeutics. A critical appraisal of novel technologies, intranasal products or medical devices available commercially has also been presented. Finally, it could be warranted that more reminiscent pharmacokinetic/pharmacodynamic relationships or validated computational models are mandated to obtain effective screening of molecular architecture of drug-polymer-mucin complexes for clinical translation of N2B therapeutic systems from bench to bedside.

For the past few years, there has been a surge in the use of nutraceuticals. The global nutraceuticals market in 2020 was USD 417.66 billion, and the market value is expected to increase by 8.9% compound annual growth rate from 2020 to 2028. This is because nutraceuticals are used to treat and prevent various diseases such as cancer, skin disorders, gastrointestinal, ophthalmic, diabetes, obesity, and central nervous system-related diseases. Nutritious food provides the required amount of nutrition to the human body through diet, whereas most of the bioactive agents present in the nutrients are highly lipophilic, with low aqueous solubility leading to poor dissolution and oral bioavailability. Also, the nutraceuticals like curcumin, carotenoids, anthocyanins, omega-3 fatty acids, vitamins C, vitamin B12, and quercetin have limitations such as poor solubility, chemical instability, bitter taste, and an unpleasant odor. Additionally, the presence of gastrointestinal (GIT) membrane barriers, varied pH, and reaction with GIT enzymes cause the degradation of some of the nutraceuticals. Nanotechnology-based nutrient delivery systems can be used to improve oral bioavailability by increasing nutraceutical stability in foods and GIT, increasing nutraceutical solubility in intestinal fluids, and decreasing first-pass metabolism in the gut and liver. This article has compiled the properties and applications of various nanocarriers such as polymeric nanoparticles, micelles, liposomes, niosomes, solid lipid nanocarriers, nanostructured lipid carrier, microemulsion, nanoemulsion, dendrimers in organic nanoparticles, and nanocomposites for effective delivery of bioactive molecules.

Wheat is the important food grain and is cultivated in many Indian states: Punjab, Haryana, Uttar Pradesh, and Madhya Pradesh, which contributes to major crop production in India. In this study, popular statistical approach multiple linear regression (MLR) and time series approaches Time Delay Neural Network (TDNN) and ARIMAX models were envisaged for wheat yield forecast using weather parameters for a case study area, i.e., Junagarh district, western Gujarat region situated at the foot of Mount Girnar. Weather data corresponds to 19 weeks (42nd to 8th Standard Meteorological Week, SMW) during crop growing season was used for prediction of wheat yield using these statistical techniques and were evaluated for their predictive capability. Furthermore, trend analysis among weather parameters and crop yield was also carried out in this study using non-parametric Mann-Kendall test and Sen's slope method. Significant negative correlation was observed between wheat yield and some of the weekly weather variables, viz., maximum temperature (48, 49, 50, 51, 52, and 4th SMW), and total rainfall (50, 51, and 1st SMW) while positive correlation was observed with morning relative humidity (49 and 3rd SMW). Study indicated that forecast error varied from 1.80 to 10.28 in MLR, 0.79 to 7.79 in ARIMAX (2,2,2), - 3.09 to 10.18 in TDNN (4,5) during model training period (1985-2014). The MAPE value shows that the time series data predicted less than 5% of variation, whereas the conventional MLR technique indicated more than 7% variation. Both ARIMAX and TDNN approaches indicated better performance during model training periods, i.e., 1985-2014 and 1985-2015, while former performed well during the forecast periods 1985-2016 and 1985-2017. Overall, the study indicated that the ARIMAX approach can be used consistently for 4 years using the same model.

The non-structural proteins (nsPs) of the chikungunya virus (CHIKV) form the virus’s replication complex. They are known to participate in several functions that allow efficient replication of the virus in diverse host systems. One such function is evading the host defense system such as RNA interference (RNAi). Two nsPs of CHIKV, namely, nsP2 and nsP3, were found to suppress the host/vector RNAi machinery and exhibit RNAi suppressor activity. The present study was undertaken to identify interacting partners of CHIKV-nsP3 in Aedes aegypti. We performed pull-down assays with the mass spectrometry approach and showed the interaction of CHIKV-nsP3 with several Aedes proteins. Further co-immunoprecipitation assays revealed that CHIKV-nsP3 interacts with RM62F, a DEAD-box containing RNA known to play roles in multiple gene regulatory processes such as alternative splicing, RNA release, and also is a component of Ago2-RISC complex.

The present study aimed to develop a novel therapeutic approach for controlled delivery of exemestane (EXE) to cancer cells using nanostructured polymeric micelles. A simplex centroid design of experiment study was employed for optimizing the polymeric micelle formulation to achieve the desired critical quality attributes, including micelle size, drug loading (DL), encapsulation efficiency (EE), and critical micelle concentration (CMC). The oil-in-water (o/w) solvent evaporation method was used to prepare mixed micelles (MMs) of copolymers L121/F127/GL44 for encapsulating EXE. Profile analysis tensiometer methods were used to determine the CMC of the copolymer mixture. EXE-MMs, blank mixed micelles, and lyophilized mixed micelles (Lyp-EXE-MMs) were characterized for other key quality attributes, such as zeta potential, chemical interactions, and morphology. The optimized ratio of L121/F127/GL44 was 1.98, 0.812, and 1.20, respectively, providing EXE-MMs with small micelle sizes (35.45 ± 1.20 nm), higher EE (89.75 ± 2.14%), and DL (5.85 ± 2.14%). EXE-encapsulated MMs exhibited an in vitro sustained release profile with improved cytotoxicity against MCF-7 cells than that with pure EXE. The cellular growth inhibitory concentration (IC50) of EXE-MMs was 0.225 ± 0.124 µg/ml, while that of naive EXE was 7.58 ± 0.145 μg/ml. Moreover, in vivo pharmacokinetic parameters of EXE micellar formulation showed significant improvement in Cmax and AUC(0–72 h), viz. 207.54 ± 18.65 ng/ml and 3530.77 ± 212.25 ng h/ml, respectively, suggesting enhanced bioavailability than that of pure EXE. EXE-MMs have a great potential for enhancing the bioavailability of EXE.

Therapeutic options for Parkinson's disease (PD) are limited to a symptomatic approach, making it a global threat. Targeting aggregated alpha-synuclein (α-syn) clearance is a gold standard for ameliorating PD pathology, bringing autophagy into the limelight. Expression of autophagy related genes are under the regulation by histone modifications, however, its relevance in PD is yet to be established. Here, preformed fibrillar form (PFF) of α-syn was used to induce PD in wistar rats, which were thereafter subjected to treatment with trehalose (tre, 4g/kg, orally), a potent autophagy inducer and sodium butyrate (SB, 300 mg/kg, orally), a pan histone deacetylase inhibitor alone as well as in combination. The combination treatment significantly reduced motor deficits as evidenced after rotarod, narrow beam walk, and open field tests. Novel object location and recognition tests were performed to govern cognitive abnormality associated with advanced stage PD, which was overcome by the combination treatment. Additionally, with the combination, the level of pro-inflammatory cytokines were significantly reduced, along with elevated levels of dopamine and histone H3 acetylation. Further, mRNA analysis revealed that levels of certain autophagy related genes and proteins implicated in PD pathogenesis significantly improved after administration of both tre and SB. Immunofluorescence and H&E staining in the substantia nigra region mirrored a potential improvement after treatment with both tre and SB. Therefore, outcomes of the present study were adequate to prove that combinatorial efficacy with tre and SB may prove to be a formidable insight into ameliorating PD exacerbated by PFF α-syn as compared to its individual efficacy.

PurposeThe requirement of high-quality government-supported healthcare services has necessitated the significance of recognizing new management practices to enhance patient satisfaction. Hence, the purpose of this study is to address the patient's enhanced custom needs through the implementation of supply chain value stream mapping (SCVSM) in government-supported drug distribution system (DDS) for enhanced patient's satisfaction.Design/methodology/approachThis study elucidates the role of one popular emerging management technique (i.e. SCVSM) in the healthcare sector by an investigative case study. The DDS in Rajasthan (India) was selected for this study. The data for this analysis were gathered in three ways (i.e. direct observation, documentary analysis and semi-structured interviews).FindingsThe outcome of this current study reveals that it is possible to apply the tool (SCVSM) to investigate the wastes in DDS to deliver the medicines at right time, right quantity and right quality. The application of SCVSM concluded that the various Kaizens (areas needed to improve) in lead time; transportation and routing should be adopted. The study further implemented kaizen on the current SCVSM and developed future SCVSM.Research limitations/implicationsAlthough various stages and functions exist in the healthcare supply chain, the current study is focused on the distribution system of drugs. The proposed approach provides a platform for both researchers and academicians to understand the existing DDS and to implement the SCVSM approach in the healthcare environment. The results show that the proposed SCVSM model is able to identify some operational bottlenecks and wastes which interfere in DDS.Originality/valueIt was observed that limited literature related to lean implementation on DDS and implementation of SCVSM on the healthcare environment in general and government-supported or public in specific are available. The current study on the application of SCVSM in DDS is unique in nature and will definitely add value to the existing literature of the application of value stream mapping (VSM) on the healthcare supply chain management field.

PurposeThe purpose of this study is to develop a methodology for the identification, categorization and prioritization of operational government-supported healthcare supply chain barriers (GHSCBs).Design/methodology/approachThis study develops a theoretical background for identifying and segregating relevant GHSCBs and proposes a 5W2H (a Toyota production system) with fuzzy DEcision MAking Trial and Evaluation Laboratory (DEMATEL) embedded approach to quantify the causal–effect relationships among the identified operational GHSCBs.FindingsSeven GHSCBs (i.e. uncertainty of demand management, lack of continuous improvement and learning, lack of deadline management, lack of social audit, warehousing equipment unavailability, human resource shortage and inadequate top level monitoring) were identified as significant cause group where the government, top management and decision-makers of government-supported healthcare supply chain (GHSC) have to put efforts.Research limitations/implicationsThe results obtained are specific to the GHSC of Indian perspective, which could be extended to global context. However, the proposed approach can be a base and provide a platform to understand and analyze the interactions among GHSCBs.Practical implicationsThe proposed methodology will show the appropriate areas for allocating efforts and resources to mitigate the impact of GHSCBs for successful implementation of healthcare supply chain.Originality/valueAccording to best of the authors' knowledge, this is the first study of operational barrier for GHSC in India in specific. The use of 5W2H embedded fuzzy DEMATEL approach for the development and analysis of the theoretical framework of Indian GHSCBs is unique in barrier literature.

Anomalies in brain insulin signaling have been demonstrated to be involved in the pathology of Alzheimer disease (AD). In this context, the neuroprotective efficacy of an insulin sensitizer, rosiglitazone, has been confirmed in our previous study. In the present study, we hypothesize that a combination of an epigenetic modulator, vorinostat, along with rosiglitazone can impart improved gene expression of neurotrophic factors and attenuate biochemical and cellular alteration associated with AD mainly by loading these drugs in a surface modified nanocarrier system for enhanced bioavailability and enhanced therapeutic efficacy. Hence, in this study, rosiglitazone and vorinostat were loaded onto a poloxamer stabilized polymeric nanocarrier system and administered to mice in the intracerebroventricular streptozotocin (3 mg/kg) induced model of AD. Treatment with the free drug combination (rosiglitazone 5 mg/kg, vorinostat 25 mg/kg) for 3 weeks attenuated the behavioral, biochemical, and cellular alterations as compared to either treatment alone (rosiglitazone 10 mg/kg, vorinostat 50 mg/kg). Further, the coencapsulated nanoformulation (rosiglitazone 5 mg/kg, vorinostat 25 mg/kg) exerted better neuroprotective efficacy than the free drug combination as evidenced by improved behavioral outcome, reduced oxidative stress, and elevated levels of neurotrophic factors. In conclusion, the synergistic neuroprotective efficacy of rosiglitazone and vorinostat has been increased through the poloxamer stabilized polymeric nanocarrier system.