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Pharmacological evaluation of vanillic acid in rotenone-induced Parkinson's disease rat model

Sharma N, Khurana N, Muthuraman A, Utreja P

Eur J Pharmacol, 2021 Jul 15;903:174112.
PMID: 33901458 DOI: 10.1016/j.ejphar.2021.174112

In the present study, we investigated the anti-Parkinson's effect of vanillic acid (VA) (12 mg/kg, 25 mg/kg, 50 mg/kg p.o.) against rotenone (2 mg/kg s.c.) induced Parkinson's disease (PD) in rats. The continuous administration of rotenone for 35 days resulted in rigidity in muscles, catalepsy, and decrease in locomotor activity, body weight, and rearing behaviour along with the generation of oxidative stress in the brain (rise in the TBARS, and SAG level and reduced CAT, and GSH levels). Co-treatment of VA and levodopa-carbidopa (100 mg/kg + 25 mg/kg p.o.) lead to a significant (P
Effect of bidi cigarette smoking on interleukin-1β and 8 levels in chronic periodontitis patient

Nath S, Prakash J, Prajapati VK, Sharma N, Pulikkotil SJ

Indian J Dent Res, 2020 8 10;31(3):433-438.
PMID: 32769279 DOI: 10.4103/ijdr.IJDR_783_17

Introduction: Bidi, a leaf rolled cigarette, is the most popular form of smoking in India. Bidi cigarette contains higher tar, ammonia, and nicotine content than a conventional cigarette and is more hazardous.
Aim of Study: The aim of this study was to determine the effect of bidi smoking on periodontitis by assessing the interleukin (IL)-1β and IL-8 from a gingival crevicular fluid (GCF).
Materials and Methods: A total of 60 patients were selected, which included 40 patients diagnosed with chronic periodontitis (20 bidi smokers and 20 non-bidi smokers) and 20 periodontal healthy controls. Diseased and healthy sites were selected from each of the chronic periodontitis subjects. Clinical parameters assessed were plaque index (PI), gingival index (GI), periodontal probing depth (PPD), recession (RC), and clinical attachment level (CAL). Pooled GCF samples were taken from the same site and analyzed for IL-1β and IL-8 using enzyme-linked immunosorbent assay.
Results: Bidi smokers displayed decreased levels of IL-1β and IL-8 than non-bidi smokers for both healthy and diseased sites and significantly reduced IL-8 levels among bidi smokers when compared to controls. Among bidi smokers, the diseased site had significantly higher levels of IL-8 than the healthy site. Non-smoker subjects with chronic periodontitis especially diseased sites contained significantly higher amounts of IL-1β and IL-8 than smokers and controls. The PI scores were highest among bidi smokers with reduced BOP and GI scores.
Conclusions: Bidi smoking influenced the cytokine profile among periodontitis patients exhibiting decreased levels of IL-1β and IL-8.
In-vitro meat: a promising solution for sustainability of meat sector

Kumar P, Sharma N, Sharma S, Mehta N, Verma AK, Chemmalar S, et al.

J Anim Sci Technol, 2021 Jul;63(4):693-724.
PMID: 34447949 DOI: 10.5187/jast.2021.e85

The in-vitro meat is a novel concept in food biotechnology comprising field of tissue engineering and cellular agriculture. It involves production of edible biomass by in-vitro culture of stem cells harvested from the muscle of live animals by self-organizing or scaffolding methodology. It is considered as efficient, environmental friendly, better ensuring public safety and nutritional security, as well as ethical way of producing meat. Source of stem cells, media ingredients, supply of large size bioreactors, skilled manpower, sanitary requirements, production of products with similar sensory and textural attributes as of conventional meat, consumer acceptance, and proper set up of regulatory framework are challenges faced in commercialization and consumer acceptance of in-vitro meat. To realize any perceivable change in various socio-economic and environmental spheres, the technology should be commercialized and should be cost-effective as conventional meat and widely accepted among consumers. The new challenges of increasing demand of meat with the increasing population could be fulfill by the establishment of in-vitro meat production at large scale and its popularization. The adoption of in-vitro meat production at an industrial scale will lead to self-sufficiency in the developed world.
Nanostructured lipid carrier to overcome stratum corneum barrier for the delivery of agomelatine in rat brain; formula optimization, characterization and brain distribution study

Ahmed S, Mahmood S, Danish Ansari M, Gull A, Sharma N, Sultana Y

Int J Pharm, 2021 Sep 25;607:121006.
PMID: 34391848 DOI: 10.1016/j.ijpharm.2021.121006

The current work attempted to achieve bypassed hepatic metabolism, controlled release, and boosted brain distribution of agomelatine by loading in NLC and administering via transdermal route. Agomelatine-loaded NLC (AG-NLC) was fabricated employing melt-emulsification technique and optimized using central composite design. The optimized AG-NLC had 183.16 ± 6.82 nm particle size, 0.241 ± 0.0236 polydispersity index, and 83.29 ± 2.76% entrapment efficiency. TEM and FESEM visually confirmed the size and surface morphology of AG-NLC, respectively. DSC thermogram confirmed the conversion of AG from crystalline to amorphous form, which indicates improved solubility of AG when loaded in NLC. For further stability and improved applicability, AG-NLC was converted into a hydrogel. The texture analysis of AG-NLC-Gel showed appropriate gelling property in terms of hardness (142.292 g), cohesiveness (0.955), and adhesiveness (216.55 g.sec). In comparison to AG-suspension-Gel (38.036 ± 6.058%), AG-NLC-Gel (89.440 ± 2.586%) exhibited significantly higher (P
Fulltext Impact of a training program on disaster preparedness among paramedic students of a tertiary care hospital of North India: A single-group, before-after intervention study

Bhattacharya S, Singh A, Semwal J, Marzo RR, Sharma N, Goyal M, et al.

J Educ Health Promot, 2020;9:5.
PMID: 32154300 DOI: 10.4103/jehp.jehp_423_19

INTRODUCTION: Disaster can occur at any time any place. Disaster preparedness plays an important role to reduce the loss of a community/country. The aim of this interventional study was to ascertain the impact of a video-based educational intervention program on improvement in knowledge and attitude of paramedical students in a hospital.
MATERIALS AND METHODS: A pre-post study (interventional study design) was conducted on paramedic students. Our study period was 6 months which was divided into Phases I, II, and III. For administrative purpose, we included all paramedical students, and our sample size was 119. The baseline assessment of knowledge and attitude of paramedic students was done by a pretested questionnaire (Observation 1) with having a baseline scoring. After that, intervention Phase 1 was implemented, and later, end line observation (Observation 2) was made. Changes in knowledge and attitude were observed by the score difference (Observation 2-Observation 1). Descriptive statistics were calculated, and the mean of cumulative score was compared using the Wilcoxon signed-rank test. We applied Mann-Whitney U-test for finding associations between dependent variables with an independent variable using SPSS version 22 (IBM, Chicago, USA) software.
RESULTS: Our baseline results showed that most of our participants had average knowledge (54.6%), followed by poor knowledge (24.4%). Approximately one-fifth (21.0%) of the participants had good knowledge regarding disaster preparedness. A significant improvement was observed in cumulative score (P < 0.005). A significant difference was observed in knowledge and attitude with respect to age and courses (P < 0.05). Forty percent of the students responded that they would like to get trained by that mock drill, and 26.1% were interested in disaster preparedness workshops in the future.
CONCLUSION: Our present study results indicate that the overall knowledge and attitude level of the students was average and required improvement. A similar result was reported in some studies conducted globally for the same purpose. All of our students perceived that training for disaster preparedness is necessary for all health facilities, and it is important to have an emergency plan and disaster management committee. Regarding training methods, most of our students liked our interactive audiovisual method. However, their preferred methods were mock drill and workshops. It can be arranged in the future for them.
Potential anti-epileptic phytoconstituents: An updated review

Kaur J, Famta P, Famta M, Mehta M, Satija S, Sharma N, et al.

J Ethnopharmacol, 2021 Mar 25;268:113565.
PMID: 33166627 DOI: 10.1016/j.jep.2020.113565

ETHNOPHARMACOLOGICAL RELEVANCE: Epilepsy is one of the most commonly occurring non-communicable neurological disorder that affects people of all age groups. Around 50 million people globally are epileptic, with 80% cases in developing countries due to lack of access to treatments determined by high cost and poor availability or it can be defined by the fraction of active epileptic patients who are not appropriately being treated. The availability of antiepileptic drugs and their adjuvant therapy in such countries is less than 50% and these are highly susceptible to drug interactions and severe adverse effects. As a result, the use of herbal medicine is increasingly becoming popular.
AIM OF THE STUDY: To provide pharmacological information on the active constituents evaluated in the preclinical study to treat epilepsy with potential to be used as an alternative therapeutic option in future. It also provides affirmation for the development of novel antiepileptic drugs derived from medicinal plants.
MATERIALS AND METHODS: Relevant information on the antiepileptic potential of phytoconstituents in the preclinical study (in-vitro, in-vivo) is provided based on their effect on screening parameters. Besides, relevant information on pharmacology of phytoconstituents, the traditional use of their medicinal plants related to epilepsy and status of phytoconstituents in the clinical study were derived from online databases, including PubMed, Clinicaltrial. gov, The Plant List (TPL, www.theplantlist.org), Science Direct. Articles identified using preset searching syntax and inclusion criteria are presented.
RESULTS: More than 70% of the phytoconstituents reviewed in this paper justified the traditional use of their medicinal plant related to epilepsy by primarily acting on the GABAergic system. Amongst the phytoconstituents, only cannabidiol and tetrahydrocannabinol have been explored for clinical application in epilepsy.
CONCLUSION: The preclinical and clinical data of the phytoconstituents to treat epilepsy and its associated comorbidities provides evidence for the discovery and development of novel antiepileptic drugs from medicinal plants. In terms of efficacy and safety, further randomized and controlled clinical studies are required to understand the complete pharmacodynamic and pharmacokinetic picture of phytoconstituents. Also, specific botanical source evaluation is needed.
Fulltext Preparation and Evaluation of the ZnO NP-Ampicillin/Sulbactam Nanoantibiotic: Optimization of Formulation Variables Using RSM Coupled GA Method and Antibacterial Activities

Sharma N, Singh V, Pandey AK, Mishra BN, Kulsoom M, Dasgupta N, et al.

Biomolecules, 2019 11 21;9(12).
PMID: 31766572 DOI: 10.3390/biom9120764

Nanoparticles (NPs) possessing antibacterial activity represent an effective way of overcoming bacterial resistance. In the present work, we report a novel formulation of a nanoantibiotic formed using Ampicillin/sulbactam (Ams) and a zinc oxide nanoparticle (ZnO NP). 'ZnO NP-Ams' nanoantibiotic formulation is optimized using response surface methodology coupled genetic algorithm approach. The optimized formulation of nanoantibiotic (ZnO NP: 49.9 μg/mL; Ams: 33.6 μg/mL; incubation time: 27 h) demonstrated 15% enhanced activity compared to the unoptimized formulation against K. pneumoniae. The reactive oxygen species (ROS) generation was directly proportional to the interaction time of nanoantibiotic and K. pneumoniae after the initial lag phase of ~18 h as evident from 2'-7'-Dichlorodihydrofluorescein diacetate assay. A low minimum inhibitory concentration (6.25 μg/mL) of nanoantibiotic formulation reveals that even a low concentration of nanoantibiotic can prove to be effective against K. pneumoniae. The importance of nanoantibiotic formulation is also evident by the fact that the 100 μg/mL of Ams and 25 µg of ZnO NP was required individually to inhibit the growth of K. pneumonia, whereas only 6.25 μg/mL of optimized nanoantibiotic formulation (ZnO NP and Ams in the ratio of 49.9: 33.6 in μg/mL and conjugation time of 27 h) was needed for the same.
Fulltext Diagnosis and management of latent tuberculosis infection in Asia: Review of current status and challenges

Paton NI, Borand L, Benedicto J, Kyi MM, Mahmud AM, Norazmi MN, et al.

Int J Infect Dis, 2019 Oct;87:21-29.
PMID: 31301458 DOI: 10.1016/j.ijid.2019.07.004

Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO 'End TB' targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI.
Technological interventions in improving the functionality of proteins during processing of meat analogs

Kumar P, Sharma N, Ahmed MA, Verma AK, Umaraw P, Mehta N, et al.

Front Nutr, 2022;9:1044024.
PMID: 36601080 DOI: 10.3389/fnut.2022.1044024

Meat analogs have opened a new horizon of opportunities for developing a sustainable alternative for meat and meat products. Proteins are an integral part of meat analogs and their functionalities have been extensively studied to mimic meat-like appearance and texture. Proteins have a vital role in imparting texture, nutritive value, and organoleptic attributes to meat analogs. Processing of suitable proteins from vegetable, mycoproteins, algal, and single-cell protein sources remains a challenge and several technological interventions ranging from the isolation of proteins to the processing of products are required. The present paper reviews and discusses in detail various proteins (soy proteins, wheat gluten, zein, algal proteins, mycoproteins, pulses, potato, oilseeds, pseudo-cereals, and grass) and their suitability for meat analog production. The review also discusses other associated aspects such as processing interventions that can be adapted to improve the functional and textural attributes of proteins in the processing of meat analogs (extrusion, spinning, Couette shear cell, additive manufacturing/3D printing, and freeze structuring). '.
Microbial engineering strategies for synthetic microplastics clean up: A review on recent approaches

Kumar V, Sharma N, Duhan L, Pasrija R, Thomas J, Umesh M, et al.

Environ Toxicol Pharmacol, 2023 Mar;98:104045.
PMID: 36572198 DOI: 10.1016/j.etap.2022.104045

Microplastics are the small fragments of the plastic molecules which find their applications in various routine products such as beauty products. Later, it was realized that it has several toxic effects on marine and terrestrial organisms. This review is an approach in understanding the microplastics, their origin, dispersal in the aquatic system, their biodegradation and factors affecting biodegradation. In addition, the paper discusses the major engineering approaches applied in microbial biotechnology. Specifically, it reviews microbial genetic engineering, such as PET-ase engineering, MHET-ase engineering, and immobilization approaches. Moreover, the major challenges associated with the plastic removal are presented by evaluating the recent reports available.
Fulltext Deciphering the role of nanoparticles for management of bacterial meningitis: an update on recent studies

Sharma N, Zahoor I, Sachdeva M, Subramaniyan V, Fuloria S, Fuloria NK, et al.

Environ Sci Pollut Res Int, 2021 Nov;28(43):60459-60476.
PMID: 34545518 DOI: 10.1007/s11356-021-16570-y

Meningitis is an inflammation of the protective membranes called meninges and fluid adjacent the brain and spinal cord. The inflammatory progression expands all through subarachnoid space of the brain and spinal cord and occupies the ventricles. The pathogens like bacteria, fungi, viruses, or parasites are main sources of infection causing meningitis. Bacterial meningitis is a life-threatening health problem that which needs instantaneous apprehension and treatment. Nesseria meningitidis, Streptococcus pneumoniae, and Haemophilus flu are major widespread factors causing bacterial meningitis. The conventional drug delivery approaches encounter difficulty in crossing this blood-brain barrier (BBB) and therefore are insufficient to elicit the desired pharmacological effect as required for treatment of meningitis. Therefore, application of nanoparticle-based drug delivery systems has become imperative for successful dealing with this deadly disease. The nanoparticles have ability to across BBB via four important transport mechanisms, i.e., paracellular transport, transcellular (transcytosis), endocytosis (adsorptive transcytosis), and receptor-mediated transcytosis. In this review, we reminisce distinctive symptoms of meningitis, and provide an overview of various types of bacterial meningitis, with a focus on its epidemiology, pathogenesis, and pathophysiology. This review describes conventional therapeutic approaches for treatment of meningitis and the problems encountered by them while transmitting across tight junctions of BBB. The nanotechnology approaches like functionalized polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, nanoemulsion, liposomes, transferosomes, and carbon nanotubes which have been recently evaluated for treatment or detection of bacterial meningitis have been focused. This review has also briefly summarized the recent patents and clinical status of therapeutic modalities for meningitis.
Emergence of microneedles as a potential therapeutics in diabetes mellitus

Zahoor I, Singh S, Behl T, Sharma N, Naved T, Subramaniyan V, et al.

Environ Sci Pollut Res Int, 2022 Jan;29(3):3302-3322.
PMID: 34755300 DOI: 10.1007/s11356-021-17346-0

Diabetes mellitus is a severe condition in which the pancreas produces inadequate insulin or the insulin generated is ineffective for utilisation by the body; as a result, insulin therapy is required for control blood sugar levels in patients having type 1 diabetes and is widely recommended in advanced type 2 diabetes patients with uncontrolled diabetes despite dual oral therapy, while subcutaneous insulin administration using hypodermic injection or pump-mediated infusion is the traditional route of insulin delivery and causes discomfort, needle phobia, reduced adherence, and risk of infection. Therefore, transdermal insulin delivery has been extensively explored as an appealing alternative to subcutaneous approaches for diabetes management which not only is non-invasive and easy, but also avoids first-pass metabolism and prevents gastrointestinal degradation. Microneedles have been commonly investigated in human subjects for transdermal insulin administration because they are minimally invasive and painless. The different types of microneedles developed for the transdermal delivery of anti-diabetic drugs are discussed in this review, including solid, dissolving, hydrogel, coated, and hollow microneedles. Numerous microneedle products have entered the market in recent years. But, before the microneedles can be effectively launched into the market, a significant amount of investigation is required to address the numerous challenges. In conclusion, the use of microneedles in the transdermal system is an area worth investigating because of its significant benefits over the oral route in the delivery of anti-diabetic medications and biosensing of blood sugar levels to assure improved clinical outcomes in diabetes management.
Fulltext Targeting natural products against SARS-CoV-2

Al-Harrasi A, Behl T, Upadhyay T, Chigurupati S, Bhatt S, Sehgal A, et al.

Environ Sci Pollut Res Int, 2022 Jun;29(28):42404-42432.
PMID: 35362883 DOI: 10.1007/s11356-022-19770-2

The human coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus; the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Natural products, secondary metabolites show positive leads with antiviral and immunotherapy treatments using genomic studies in silico docking. In addition, it includes the action of a mechanism targeting the SARS-CoV-2. In this literature, we aimed to evaluate the antiviral movement of the NT-VRL-1 unique terpene definition to Human coronavirus (HCoV-229E). The effects of 19 hydrolysable tannins on the SARS-CoV-2 were therefore theoretically reviewed and analyzed utilising the molecular operating surroundings for their C-Like protease 3CLpro catalytic dyad residues Angiotensin converting enzyme-2 (MOE 09). Pedunculagin, tercatan, and castalin were detected as interacting strongly with SARS-receptor Cov-2's binding site and catalytic dyad (Cys145 and His41). SARS-CoV-2 methods of subunit S1 (ACE2) inhibit the interaction of the receiver with the s-protein once a drug molecule is coupled to the s-protein and prevent it from infecting the target cells in alkaloids. Our review strongly demonstrates the evidence that natural compounds and their derivatives can be used against the human coronavirus and serves as an area of research for future perspective.
Exploring the effect of Crinum latifolia in obesity: possible role of oxidative, angiogenic, and inflammatory pathways

Nijhawan P, Behl T, Chigurupati S, Sehgal A, Singh S, Sharma N, et al.

Environ Sci Pollut Res Int, 2022 Jan 07.
PMID: 34997511 DOI: 10.1007/s11356-022-18531-5

Obesity is a multifaceted disease encompassing deposition of an unnecessary amount of fat which upsurges the possibility of other complications, viz., hypertension and certain type of cancers. Although obesity results from combination of genetic factors, improper diet and inadequate physical exercise also play a major role in its onset. The present study aims at exploring the anti-obesity activity of Crinum latifolia leaf extract in obese rats. The leaves were extracted using hydroalcoholic extraction which was later diluted with water and given to obese rats. The dosing was started from the 4th week (by oral administration of extract of Crinum latifolia (100 mg/kg and 200 mg/kg) and combination of Crinum latifolia leaf extract 200 mg/kg and orlistat 30 mg/kg) till the 10th week. Various angiogenic, antioxidant, biochemical, and inflammatory biomarkers were assessed at the end of the study. The obese symptoms were progressively reduced in treatment groups when compared to disease control groups. The angiogenic parameters and inflammatory parameters were consequently reduced in treatment groups. The oxidative parameters superoxide dismutase (SOD) and catalase were gradually increased, while levels of TBARS were reduced in treatment groups showing antioxidant nature of leaf hydroalcoholic extract. The Crinum latifolia leaf extract possesses anti-obesity properties and therefore can be used as a therapeutic option in the management of obesity.
Commercialization potential of agro-based polyhydroxyalkanoates biorefinery: A technical perspective on advances and critical barriers

Kumar V, Lakkaboyana SK, Tsouko E, Maina S, Pandey M, Umesh M, et al.

Int J Biol Macromol, 2023 Apr 15;234:123733.
PMID: 36801274 DOI: 10.1016/j.ijbiomac.2023.123733

The exponential increase in the use and careless discard of synthetic plastics has created an alarming concern over the environmental health due to the detrimental effects of petroleum based synthetic polymeric compounds. Piling up of these plastic commodities on various ecological niches and entry of their fragmented parts into soil and water has clearly affected the quality of these ecosystems in the past few decades. Among the many constructive strategies developed to tackle this global issue, use of biopolymers like polyhydroxyalkanoates as sustainable alternatives for synthetic plastics has gained momentum. Despite their excellent material properties and significant biodegradability, polyhydroxyalkanoates still fails to compete with their synthetic counterparts majorly due to the high cost associated with their production and purification thereby limiting their commercialization. Usage of renewable feedstocks as substrates for polyhydroxyalkanoates production has been the thrust area of research to attain the sustainability tag. This review work attempts to provide insights about the recent developments in the production of polyhydroxyalkanoates using renewable feedstock along with various pretreatment methods used for substrate preparation for polyhydroxyalkanoates production. Further, the application of blends based on polyhydroxyalkanoates, and the challenges associated with the waste valorization based polyhydroxyalkanoates production strategy is elaborated in this review work.
Interactions with the macrophages: An emerging targeted approach using novel drug delivery systems in respiratory diseases

Mehta M, Deeksha, Sharma N, Vyas M, Khurana N, Maurya PK, et al.

Chem Biol Interact, 2019 May 01;304:10-19.
PMID: 30849336 DOI: 10.1016/j.cbi.2019.02.021

Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages are essential in maintaining homeostatic tissue processes, repair and immunity. Also, play important role in cytokine secretion and signal transduction of the infection so as to develop acquired immunity. Accounting to their involvement in pathogenesis, macrophages present a therapeutic target for the treatment of inflammatory respiratory diseases. This review focuses on novel drug delivery systems (NDDS) including nanoparticles, liposomes, dendrimers, microspheres etc that can target alveolar macrophage associated with inflammation, intracellular infection and lung cancer. The physiochemical properties and functional moieties of the NDDS attributes to enhanced macrophage targeting and uptake. The NDDS are promising for sustained drug delivery, reduced therapeutic dose, improved patient compliance and reduce drug toxicity. Further, the review also discuss about modified NDDS for specificity to the target and molecular targeting via anti-microbial peptides, kinases, NRF-2 and phosphodiesterase.
Fulltext Mutant Allele-Specific CRISPR Disruption in DYT1 Dystonia Fibroblasts Restores Cell Function

Cruz L, György B, Cheah PS, Kleinstiver BP, Eimer WA, Garcia SP, et al.

Mol Ther Nucleic Acids, 2020 Sep 04;21:1-12.
PMID: 32502938 DOI: 10.1016/j.omtn.2020.05.009

Most individuals affected with DYT1 dystonia have a heterozygous 3-bp deletion in the TOR1A gene (c.907_909delGAG). The mutation appears to act through a dominant-negative mechanism compromising normal torsinA function, and it is proposed that reducing mutant torsinA may normalize torsinA activity. In this study, we used an engineered Cas9 variant from Streptococcus pyogenes (SpCas9-VRQR) to target the mutation in the TOR1A gene in order to disrupt mutant torsinA in DYT1 patient fibroblasts. Selective targeting of the DYT1 allele was highly efficient with most common non-homologous end joining (NHEJ) edits, leading to a predicted premature stop codon with loss of the torsinA C terminus (delta 302-332 aa). Structural analysis predicted a functionally inactive status of this truncated torsinA due to the loss of residues associated with ATPase activity and binding to LULL1. Immunoblotting showed a reduction of the torsinA protein level in Cas9-edited DYT1 fibroblasts, and a functional assay using HSV infection indicated a phenotypic recovery toward that observed in control fibroblasts. These findings suggest that the selective disruption of the mutant TOR1A allele using CRISPR-Cas9 inactivates mutant torsinA, allowing the remaining wild-type torsinA to exert normal function.
Hypoxia-Inducible Factor (HIF): Fuel for Cancer Progression

Satija S, Kaur H, Tambuwala MM, Sharma P, Vyas M, Khurana N, et al.

Curr Mol Pharmacol, 2021;14(3):321-332.
PMID: 33494692 DOI: 10.2174/1874467214666210120154929

Hypoxia is an integral part of the tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1β (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygen-independent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mechanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors.
Perfluorocarbons Therapeutics in Modern Cancer Nanotechnology for Hypoxiainduced Anti-tumor Therapy

Satija S, Sharma P, Kaur H, Dhanjal DS, Chopra RS, Khurana N, et al.

Curr Pharm Des, 2021;27(43):4376-4387.
PMID: 34459378 DOI: 10.2174/1381612827666210830100907

With an estimated failure rate of about 90%, immunotherapies that are intended for the treatment of solid tumors have caused an anomalous rise in the mortality rate over the past decades. It is apparent that resistance towards such therapies primarily occurs due to elevated levels of HIF-1 (Hypoxia-induced factor) in tumor cells, which are caused by disrupted microcirculation and diffusion mechanisms. With the advent of nanotechnology, several innovative advances were brought to the fore; and, one such promising direction is the use of perfluorocarbon nanoparticles in the management of solid tumors. Perfluorocarbon nanoparticles enhance the response of hypoxia-based agents (HBAs) within the tumor cells and have been found to augment the entry of HBAs into the tumor micro-environment. The heightened penetration of HBAs causes chronic hypoxia, thus aiding in the process of cell quiescence. In addition, this technology has also been applied in photodynamic therapy, where oxygen self-enriched photosensitizers loaded perfluorocarbon nanoparticles are employed. The resulting processes initiate a cascade, depleting tumour oxygen and turning it into a reactive oxygen species eventually to destroy the tumour cell. This review elaborates on the multiple applications of nanotechnology based perfluorocarbon formulations that are being currently employed in the treatment of tumour hypoxia.
Fulltext Botanicals and Oral Stem Cell Mediated Regeneration: A Paradigm Shift from Artificial to Biological Replacement

Ahuja A, Tyagi PK, Kumar M, Sharma N, Prakash S, Radha, et al.

Cells, 2022 Sep 07;11(18).
PMID: 36139367 DOI: 10.3390/cells11182792

Stem cells are a well-known autologous pluripotent cell source, having excellent potential to develop into specialized cells, such as brain, skin, and bone marrow cells. The oral cavity is reported to be a rich source of multiple types of oral stem cells, including the dental pulp, mucosal soft tissues, periodontal ligament, and apical papilla. Oral stem cells were useful for both the regeneration of soft tissue components in the dental pulp and mineralized structure regeneration, such as bone or dentin, and can be a viable substitute for traditionally used bone marrow stem cells. In recent years, several studies have reported that plant extracts or compounds promoted the proliferation, differentiation, and survival of different oral stem cells. This review is carried out by following the PRISMA guidelines and focusing mainly on the effects of bioactive compounds on oral stem cell-mediated dental, bone, and neural regeneration. It is observed that in recent years studies were mainly focused on the utilization of oral stem cell-mediated regeneration of bone or dental mesenchymal cells, however, the utility of bioactive compounds on oral stem cell-mediated regeneration requires additional assessment beyond in vitro and in vivo studies, and requires more randomized clinical trials and case studies.

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