A Comprehensive Examination of Heterocyclic Scaffold Chemistry for Antitubercular Activity.

Tuberculosis is a communicable disease which affects humans particularly the lungs and is transmitted mainly through air. Despite two decades of intensive research aimed at understanding and combating tuberculosis, persistent biological uncertainties continue to hinder progress. Nowadays, heterocyclic compounds have proven themselves in effective treatment of tuberculosis because of their wide range of biological and pharmacological activities. Antituberculosis or antimycobacterial agents encompass a broad array of compounds utilized singly or in conjunction to combat Mycobacterium infections, spanning from tuberculosis to leprosy. Here, we summarize the synthesis of various heterocyclic compounds which includes the greener synthetic route as well as use of nano compounds as catalyst along with their anti TB activities.

Challenges of current treatment and exploring the future prospects of nanoformulations for treatment of atopic dermatitis.

Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by a burning sensation and eczematous lesions in diverse portions of the body. The treatment of AD is exclusively focused to limit the itching, reduce inflammation, and repair the breached barrier of the skin. Several therapeutic agents for the treatment and management of AD have been reported and are in use in clinics. However, the topical treatment of AD has been an unswerving challenge for the medical fraternity owing to the impaired skin barrier function in this chronic skin condition. To surmount the problems of conventional drug delivery systems, numerous nanotechnology-based formulations are emerging as alternative new modalities for AD. Latter enhances the bioavailability and delivery to the target disease site, improves drug permeation and therapeutic efficacy with reduced systemic and off-target side effects, and thus improves patient health and promotes compliance. This review aims to describe the various pathophysiological events involved in the occurrence of AD, current challenges in treatment, evidence of molecular markers of AD and its management, combinatorial treatment options, and the intervention of nanotechnology-based formulations for AD therapeutics.

Effective utilization of discarded reverse osmosis post-carbon for adsorption of dyes from wastewater.

In this study, the deployment of post Reverse Osmosis (RO)-carbon as a adsorbent for dye removal from water has been investigated. The post RO-carbon was thermally activated (RO900), and the material thus obtained exhibited high surface area viz. 753 m2/g. In the batch system, the efficient Methylene Blue (MB) and Methyl Orange (MO) removal was obtained by using 0.08 g and 0.13 g/50 mL adsorbent dosage respectively. Moreover, 420 min was the optimized equilibration time for both the dyes. The maximum adsorption capacities of RO900 for MB and MO dyes were 223.29 and 158.14 mg/g, respectively. The comparatively higher MB adsorption was attributed to the electrostatic attraction between adsorbent and MB. The thermodynamic findings revealed the process as spontaneous, endothermic, and accompanied by entropy increment. Additionally, simulated effluent was treated, and >99% dye removal efficiency was achieved. To mimic an industrial perspective, MB adsorption onto RO900 was also carried out in continuous mode. The initial dye concentration and effluent flow rate were among the process parameters that were optimized using the continuous mode of operation. Further, the experimental data of continuous mode was fitted with Clark, Yan, and Yoon-Nelson models. Py-GC/MS investigation revealed that dye-loaded adsorbents could be pyrolyzed to produce valuable chemicals. The cost and low toxicity associated benefits of discarded RO-carbon over other adsorbents reveal the significance of the present study.

Toenail Dust as a Potential Occupational Hazard in Podiatric Medicine: A Comprehensive Literature Review.

BACKGROUND: Debridement of toenails is a common procedure that leads to the production of nail dust aerosols in the work environment. Previous studies indicate that inhaled nail dust can cause respiratory distress and eye irritation. This comprehensive review aimed to assess the available literature on the effect of nail dust exposure and to evaluate nail dust as a potential occupational hazard for podiatric physicians. METHODS: A comprehensive literature search was conducted via PubMed, Google Scholar, CINAHL, Cochrane Library, and ClinicalTrials.gov. Risks of bias of the collected studies were evaluated using various assessment tools to match the type of study design. A qualitative analysis of the included studies was performed, from which primary and secondary outcome measures were extracted: prevalence of symptoms and specific microorganisms in nail dust. RESULTS: Of 403 articles screened, eight met the inclusion criteria. The primary outcome measure resulted in a pooled prevalence of eye-related symptoms being the most consistent symptom reported (41%-48%). The secondary outcome measure resulted in a pooled prevalence of Trichophyton rubrum (9.52%-38%) and Aspergillus (11.11%-35.48%) as the most common microorganisms present in nail dust. CONCLUSIONS: From the included eight articles, we found that nail dust is a potential occupational hazard, especially for those exposed more often. Aspergillus and T rubrum are most commonly associated with nail dust leading to development of respiratory illness. It is important to take preventive measures in podiatric medical clinics by using improved and efficient personal protective equipment for workers exposed to nail dust. Detailed health safety guidelines can be developed to decrease respiratory symptoms and diseases from nail dust exposure.

Preclinical safety of tetrahydrocurcumin loaded lipidic nanoparticles incorporated into tacrolimus ointment: In vitro and in vivo evaluation.

Preclinical safety and proof of concept studies for a topical ointment comprising of concentrated tetrahydrocurcumin loaded lipidic nanoparticles (THC-LNs) and tacrolimus ointment (TTO) is proposed in the present investigation. The skin irritation potential and acute dermal toxicity were performed in rats in compliance with the Organization for Economic Cooperation and Development (OECD) guidelines (402, 404 and 410) while the cytotoxic potential was performed in HaCaT cells. Finally, in vivo evaluation was performed in Imiquimod mice model of psoriasis. In primary skin irritation assessment, TTO formulation, marketed formulation (Tacroz® Forte), THC-LNs, and blank LNs were topically applied on intact skin sites in rats while another group served as a negative control group for 72 h. TTO did not induce any adverse reactions. Repeated 28 days dermal toxicity followed by biochemical and histopathological assessment showed negligible alternations and skin lesions. THC-LNs revealed negligible cytotoxic potential in HaCaT cells. TTO showed significantly high anti-psoriatic activity in comparison to marketed ointment. This was also confirmed via histopathological evaluation. Based on these findings, it can be ascertained that TTO showed minimal toxicity and has ample potential for further clinical analysis. The above studies affirm the potential of TTO as an alternative for psoriasis.

Tetrahydrocurcumin Lipid Nanoparticle Based Gel Promotes Penetration into Deeper Skin Layers and Alleviates Atopic Dermatitis in 2,4-Dinitrochlorobenzene (DNCB) Mouse Model.

Treatment of atopic dermatitis (AD) is challenging due to its complex pathophysiology. Tetrahydrocurcumin (THC) a polyphenolic, colorless compound that is more polar than curcumin. It possesses superior anti-inflammatory properties and has a clinical advantage over curcumin. The present study investigated the therapeutic effectiveness of THC solid lipid nanoparticle (THC-SLN)-based gels in AD. THC-SLNs prepared using microemulsification resulted in a particle size of 109.2 nm as determined by nanoparticle tracking, and FTIR confirmed the entrapment of drug within the lipid matrix. THC-SLNs greatly enhanced skin hydration when tested both ex vivo and in vivo in Lacca mice. Deeper skin penetration was clearly established using dermatokinetics and CLSM. The in vivo pharmacodynamics of THC-SLNs gel in 2,4-dinitrochlorobenzene (DNCB)-induced AD mice showed enhanced bioactivity; reduced levels of TNF-α and IL-6; and complete healing, as evident from histopathological studies. Thus, the novel topical THC-SLN gel has potential to emerge as a safe alternative to conventional corticosteroids for AD and other skin disorders with overbearing inflammation.

Forensic examination of effects of Parkinsonism on various handwriting characteristics.

Parkinsonism is a neurodegenerative syndrome that causes impairment of motor skills in affected persons. Thus, adverse effects may be produced in the handwriting of persons suffering from Parkinsonism. Medication used for the treatment of Parkinsonism is known to subside certain motor defects for specific time intervals, showing slight differences or improvement in certain handwriting characteristics during those intervals on the same day as compared to the ones executed before medication. Certain handwriting characteristics affected due to Parkinsonism may be mistaken as forged features due to poor line quality, which can cause suspicion upon the authenticity of important legal documents. The present research work has been carried out to determine the effects of Parkinsonism and medication used for its treatment on handwriting. Handwriting/signature samples executed before and after the onset of Parkinsonism (both pre- and post-medication) have been randomly collected from 70 participants. These handwritings have been evaluated separately and compared inter-se for various handwriting characteristics with qualitative and statistical approach. The results have demonstrated significant changes in most of the characteristics in both affected writings of majority of participants as compared to their corresponding earlier writings. Thus, forensic document experts should be aware of the detrimental effects of Parkinsonism on handwriting in pre- and post-medication conditions of this ailment.

Co-Hydrothermal Liquefaction of algal and lignocellulosic biomass: Status and perspectives.

Hydrothermal liquefaction (HTL) effectively converts biomass to biofuels, thereby limiting the endless reliance on petroleum products derived from fossil fuels. However, the conversion is based on individual feedstock in the HTL process. In order to, further boost the conversion, HTL can be done by blending various feedstock, mainly algal and lignocellulosic biomass. Bibliometric analysis was carried out, and it was observed that there have been very few studies on Co-Hydrothermal Liquefaction (Co-HTL). There still exist several crucial gaps in process optimization when co-reactants are used due to their synergistic effects. The reaction kinetics and mechanism, catalyst screening and by-products application require further studies. Therefore, R&D is necessary to optimize the process to completely utilize the complementarity of the feedstocks under study resulting in better quality of products which require minor/ no upgradation steps.

Preparation and characterization of lignin-derived hard templated carbon(s): Statistical optimization and methyl orange adsorption isotherm studies.

In this study, lignin-derived zeolite templated carbon materials were fabricated to remove the organic contaminant, methyl orange. Response surface methodology with Box-Behnken design was used to optimize the adsorption parameters. Based on Box-Behnken design, a quadratic model was developed to correlate the adsorption variables with the response, removal efficiency. Analysis of variance revealed the adsorbent dosage as the most influential adsorption variable. Lignin derived ZSM-5 (PZ) and mordenite (PM) templated carbon materials exhibited high surface area; 476.0 and 716.0 m2/g respectively. The maximum theoretical adsorption capacity of PZ and PM for methyl orange was 514.0 and 225.0 mg/g, respectively. The experimental kinetic data best fitted to pseudo-second-order model for both the adsorbents. PZ adsorbent was also utilized to treat real wastewater containing dyes and achieved 40 % methyl orange removal efficiency. Adsorption thermodynamic study revealed the process as spontaneous, exothermic and also indicated the increment in entropy after adsorption.

Assay and Dermatokinetics of Tetrahydrocurcumin Lipidic Nanostructures Using Reverse Phase-high Performance Liquid Chromatography.

BACKGROUND: Envisaging the poor solubility (56 ngml1) and permeability of tetrahydrocurcumin (THCC), it was formulated into lipidic nanostructures to enhance its bioavailability upon topical application to promote the healing process for skin inflammatory disorders. Lack of literature on a suitable method for determining THCC per se and nanoformulations prompted us to develop an RP-HPLC method to detect the drug in its nanostructures and in pig ear skin post dermatokinetics. OBJECTIVE: The present investigation aimed to develop a simple, precise and RP-HPLC method for the quantitative estimation of THCC in prepared lipidic nanostructures, its ointment, and in skin homogenate obtained post dermatokinetic study. METHODS: THCC encapsulated nanostructures and ointment were formulated using a modified emulsification method and embedded into an ointment base to enhance its spreadability and improve patient compliance. A fast and sensitive reverse-phase high-performance liquid chromatography method was developed using a Hypersil BDS reverse phase C18 column (4.6 mm × 250 mm, 5 µm) with mobile phase comprising tetrahydrofuran (THF) and 1 mgmL-1 citric acid (4:6), at a flow rate of 1.0 mLmin-1 with a run time of 20 min. RESULTS: THCC nanostructures were successfully prepared using the spontaneous microemulsification method. THCC was detected at 282 nm and revealed two peaks which were attributed to the keto-enol tautomerism in the molecule with retention times of 6.23 min and 11.06 min, respectively. The assay of THCC in nanostructures and ointment was found to be 98.30 % and 99.98 %, with an entrapment efficiency 77.00±2.74 %. The dermatokinetic studies revealed sufficient release of THCC from its ointment up to 24 hr with a concentration of 1382 µgcm-2, for causing a therapeutic effect. CONCLUSION: The method was found to be reproducible and robust, as shown by the low coefficient of variation and a constant analyte/IS ratio. It was successfully employed for the estimation of THCC assay in nanostructures and its ointment and dermatokinetic analysis in the skin.

Dithranol: An Insight into its Novel Delivery Cargos for Psoriasis Management.

OBJECTIVE: Dithranol (DTH) is a well-known moiety that has long been used promisingly to impede and treat skin disorders, particularly psoriasis. Nowadays, a rekindled interest in the use of DTH for this disorder has been observed. Side effects associated with conventional topical formulations of this moiety have aroused the interest of the scientific community in investigating novel cargos of DTH for psoriasis management. RESULTS: Previous research has evidenced the anti-inflammatory and anti-proliferating potential of DTH. Numerous studies have indicated that DTH inhibits polymorphonuclear (PMN) leucocyte, modulates epidermal cell receptors and promotes anti-psoriatic action. However, some deterrent factors like poor solubility, stability, toxicity, staining and skin irritation hamper its use as a potential therapeutic agent. With the adoption of novel drug delivery technologies, the above mentioned inherent limitations of DTH have been compensated to reestablish this drug moiety. CONCLUSION: This article reviews novel drug delivery aspects, safety concerns, clinical evidence, current status, and future opportunities of DTH in the management of psoriasis. Further, it will update researchers on this promising drug moiety, which is free from systemic adverse responses in comparison to other therapeutic molecules like steroids, for psoriasis treatment.

Hydochar and biochar: Production, physicochemical properties and techno-economic analysis.

Utilization of natural, abundant, and renewable resources for the production of carbon materials with simple and energy-efficient processes is an upsurge interest. The production processes and resultant biochar can address widespread concerns such as climate change, energy crisis, and environmental pollution. The properties of produced chars (biochar/hydrochar) depend on the production methods, feedstock, and operating parameters, which significantly affect their use for various applications. In this review, production, physiochemical properties, and techno-economic analysis of chars are summarized. This review provides the fundamentals and reaction mechanism of char production methodologies. Physicochemical properties based on chemical composition, functional groups, structure, porosity, and shapes have been compared. The effects of operating parameters on the physicochemical properties of chars are discussed. In addition, this review offers insights on new directions for char production and research in the future, based on the updated and detailed investigation of energy balance with economy of char production methodologies.

Solid base catalytic hydrothermal liquefaction of macroalgae: Effects of process parameter on product yield and characterization.

The hydrothermal liquefaction (HTL) of Sargassum tenerrimum (ST) macroalgae was carried out for 15 min, over various solid base catalysts (CaO supported on CeO2, Al2O3, and ZrO2) at different reaction temperatures (260-300 °C), different catalyst quantities (5-25 wt%) and using different solvent systems. Maximum bio-oil (BO) yields for the non-catalytic HTL with single solvent water, ethanol, and water-ethanol co-solvent were 3.3 wt%, 23.3 wt%, and 32.0 wt%, respectively, at 280 °C. Ethanol as single solvent elicited highest BO yield of 25.2 wt% with CaO/ZrO2 (10.0 wt%) catalyst. However, the highest BO yield (33.0 wt%) accompanied by higher conversion (70.5%) was obtained with CaO/ZrO2 (10.0 wt%) under water-ethanol co-solvent. The selectively higher percentage of ester functional compounds (87.8%) was found with CaO/ZrO2 catalyst under water-ethanol co-solvent. Also, the bio-oil obtained from catalytic liquefaction showed a higher high heating value (HHV) compared to that from the non-catalytic HTL reaction.

Determination of the Chronological Order of a Laser Printing and Gel Pen Writing Without any Crossing Strokes.

Laser printers and writing instruments are being exploited by the forgers to produce fabricated documents. They often produce such documents by appending genuine signature on a blank sheet and later printing on it. Often these fabricated documents do not contain intersection of strokes and may pose a difficulty to forensic document examiners in analyzing cases related to such documents. Keeping in mind the limited research work done on nonintersecting strokes, the present study has been conducted with an aim to determine the sequence of nonintersecting strokes of gel pens and laser printers. Three hundred samples of nonintersecting strokes of gel pen ink and laser printing were prepared. Of these 300, 150 had laser-printed text below the gel pen strokes and the remaining 150 were prepared with gel pen stokes below the laser-printed text. The samples have been analyzed using Nikon SMZ 800N stereomicroscope. Three micro-conformation features, that is, pattern of toner distribution, ink distribution, and fiber distribution have been observed in the samples. The results demonstrate the successful establishment of sequence of nonintersecting strokes in case of gel pen and laser-printed documents by the determination of micro-conformation features.

Advances in design strategies for preparation of biochar based catalytic system for production of high value chemicals.

The aim of this review is to provide the comprehensive and mechanistic information of biochar based catalytic systems for the production of fuels and fine chemicals with a concept of integrated biorefinery. The review presents an in-depth assessment of relationships between physico-chemical properties and catalytic performances of biochar based catalytic systems during the production of targeted compounds at the molecular/fundamental level. The catalytic performance of the biochar is associated with its unique physico-chemical properties (surface area/surface functionality/pores/mechanical strength/inorganic species) which provide a distinct catalytic route. The review also discusses the preparation methods and significance of the activation process for tuning of physico-chemical properties of biochar.

Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature.

Oral Cancer (OC) is a serious and growing problem which constitutes a huge burden on people in more and less economically developed countries alike. The scenario is clearly depicted from the increase in the expected number of new cases in the US diagnosed with OC from 49,670 people in 2016, to 49,750 cases in 2017. The situation is even more alarming in India, with 75,000 to 80,000 new cases being reported every year, thus making it the OC capital of the world. Leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, discoid lupus erythmatosus, hereditary disorders such as dyskeratosis congenital and epidermolisys bullosa are highlighted by WHO expert working group as the predisposing factors increasing the risk of OC. Consumption of tobacco and alcohol, genetic factors, and human papilloma virus are assigned as the factors contributing to the aetiology of OC. On the other hand, pathogenesis of OC involves not only apoptosis but also pain, inflammation and oxidative stress. Inspite of current treatment options (surgery, radiotherapy, and chemotherapy), OC is often associated with recurrence and formation of secondary primary tumours resulting in poor overall survival rates (∼50%). The intervention of nano technology-based drug delivery systems as therapeutics for cancers is often viewed as a cutting edge for technologists. Though ample literature on the usefulness of nano-coutured cancer therapeutics, rarely any product is in pipeline. Yet, despite all the hype about nanotechnology, there are few ongoing trials. This review discusses the current and future trends of nano-based drug delivery for the treatment of OC.

Topical delivery of tetrahydrocurcumin lipid nanoparticles effectively inhibits skin inflammation: in vitro and in vivo study.

Tetrahydrocurcumin (THC) also referred to as 'white curcumin', is a stable colorless hydrogenated product of curcumin with superior antioxidant and anti-inflammatory properties. The present study is an attempt to elevate the topical bioavailability of THC, post-incorporation into a nano-carrier system with its final dosage as a hydrogel. Lipid nanoparticles of THC (THC-SLNs) prepared by microemulsification technique were ellipsoidal in shape (revealed in transmission electron microscopy) with a mean particle size of 96.6 nm and zeta potential of -22 mV. Total drug content and entrapment efficiency of THC-SLNs was 94.51% ± 2.15% and 69.56% ± 1.35%, respectively. Differential scanning calorimetry and X-ray diffraction studies confirmed the formation of THC-SLNs. In vitro drug release studies showed the drug release from THC-SLNs gel to follow Higuchi's equation revealing a Fickian diffusion. Ex vivo permeation studies indicated a 17 times (approximately) higher skin permeation of THC-SLNs gel as compared with the free THC gel. Skin irritation, occlusion, and stability studies indicated the formulation to be nonirritating, and stable with a desired occlusivity. Pharmacodynamic evaluation in an excision wound mice model clearly revealed the enhanced anti-inflammatory activity of THC-SLNs gel and was further confirmed using biochemical and histopathological studies. It is noteworthy to report here that THC-SLNs gel showed significantly better (p ≤ 0.001) activity than free THC in gel. As inflammation is innate to all the skin disorders, the developed product opens up new therapeutic avenues for several skin diseases. To the best of our knowledge, this is the first paper elaborating the therapeutic usefulness of white curcumin-loaded lipidic nanoparticles for skin inflammation.

Mapping natural radioactivity of soil samples in different regions of Punjab, India.

Thallium activated sodium iodide (NaI(Tl)) detector and multi channel analyzer has been utilized to measure gamma rays emitted by radio nuclides found in soil samples of south-west (SW) region of Punjab state, India where elevated level of uranium of around value of 700µg/l in groundwater has been reported. For comparative study, soil samples were also collected and analyzed from west (W) and north east (NE) regions of the state. Uranium and potassium has been found to be comparatively higher in SW region whereas thorium level is higher in W and NE part of Punjab state. Overall concentration level of naturally occurring radio nuclides 40K, 238U and 232Th has been found to be varied from 260.1±17.3 to 728.2±27.7, BDL to 41.9±10.3 and 29.5±7.1 to 88.1±6.2Bq/Kg respectively. Overall average level of 40K and 232Th has been found to be higher as compared to world's average concentration level. Average radium equivalent activity (134.8±23.03 (σ) Bq/Kg), dose rate (61.9±10.3nGy/h), outdoor and indoor dose (0.30±0.05 and 0.08±0.01 mSv/year), external and internal hazard index (0.36±0.06 and 0.42±0.08) has been calculated.