Whole genome sequencing (WGS) of Mycobacterium tuberculosis has been constructive in understanding its evolution, genetic diversity and the mechanisms involved in drug resistance. A large number of sequencing efforts from across the globe have revealed genetic diversity among clinical isolates and the genetic determinants for their resistance to anti-tubercular drugs. Considering the high TB burden in India, the availability of WGS studies is limited. Here we present, WGS results of 200 clinical isolates of M. tuberculosis from North India which are categorized as sensitive to first-line drugs, mono-resistant, multi-drug resistant and pre-extensively drug resistant isolates. WGS revealed that 20% of the isolates were co-infected with M. tuberculosis and non-tuberculous mycobacteria species. We identified 12,802 novel genetic variations in M. tuberculosis isolates including 343 novel SNVs in 38 genes which are known to be associated with drug resistance and are not currently used in the diagnostic kits for detection of drug resistant TB. We also identified M. tuberculosis lineage 3 to be predominant in the northern region of India. Additionally, several novel SNVs, which may potentially confer drug resistance were found to be enriched in the drug resistant isolates sampled. This study highlights the significance of employing WGS in diagnosis and for monitoring further development of MDR-TB strains.
Rumex hastatus (Polygonaceae) Naphthalene acylglucosides, rumexneposides. 88 Salvia hypargeia (Lamiaceae) Diterpenoids (Labdane), hypargenin 89-92 Senecio chionophilus (Asteraceae) Sesqui terpenoids (oxofuranoeremophilane) 93,94 Vitex trifolia (Verbenaceae) Diterpenoids (halimane and labdane) 1,95 Vitex negundo (Verbenaceae) Iridoid glycosides, isomeric flavanones and flavonoids 96,97 Juniperus communis (Cuppressaceae) Isocupressic acid, communic acid and deoxypodophyllotoxin 98,99 Monoterpenoids Cymbopogon (lemon grass). Citronellol, nero, dehydro costuslactone 100 Sesquiterpenes Saussurea lappa (Compositae) Costunolide 101 Magnolia grandiflora (Magnoliaceae) Parthenolide 101 Ambrosia artemisiifolia (Asteraceae) 11bH-dihydroparthenolide 101 Ambrosia confertiflora (Asteraceae) Santamarine 101 Sonchus hierrensis (Asteraceae) Santamarine 101 Ambrosia confertiflora (Asteraceae) Reynosin 101 Artemisia ramose (Compositae) Santonin 101 Podachenium eminens (Asteraceae) 7-hydroxydehydrocostuslactone 102 Zaluzania triloba (Compositae]) Zaluzanin C 101 Diterpenes Tetradenia riparia (Lamiaceae) Sandaracopimara-8(14)-15-diene-7a,18-dio 103 Juniperus excels (Cupressaceae) Sandracopimaric acid, juniperexcelsic acid 104
a b s t r a c tAim: To isolate and identify the quercetin from polyherbal hepatoprotective formulation. Polyherbal formulations were developed by using five bioactive fractionated extracts of Butea monosperma, Bauhinia variegata and Ocimum gratissimum for treatment of liver disorders by exploiting the knowledge of traditional system of medicine and evaluated for hepatoprotective activity using acute liver toxicity model of paracetamol induced liver damage in rats. Methods: Major active fractions were isolated by solvent fractionation and quantified by HPTLC method. Two polyherbal tablet formulations were developed by the wet granulation method using microcrystalline cellulose, aerosil and other excipients and subjected for physicochemical evaluation to assess physical stability followed by pharmacological screening. The prepared tablets were finally subjected to stability testing to assess its shelf-life. The rats were monitored for change in liver morphology, biochemical parameters like serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP) and total bilirubin for polyherbal tablet formulation at 50 mg/kg and polyherbal tablet formulation at 100 mg/kg. Results: Active principle was isolated, quantified by HPTLC and characterized with IR. Both formulations showed significant hepatoprotective activity. The histological studies were also support the biochemical parameters. From the results of biochemical analysis and histopathological studies, it can be accomplished that polyherbal tablet formulation at 100 mg/kg can be effectively formulated into a suitable dosage form with added benefit of no side effects for control and cure of chronic ailments like liver disorders. A comparative histopathological study of liver exhibited almost normal architecture as compared to toxicant group. Conclusion: Biochemical marker showed improved results for polyherbal tablet formulation at 100 mg/ kg. Polyherbal tablet formulation contains a potent hepatoprotective agent suggested to be a flavone concentrated in polyherbal formulation which may find clinical application in amelioration of paracetamol induced liver damage.
Solid lipid nanoparticles are one of the developed technologies for addressing the bioavailability and targeting issues of drug delivery. In this review article, we attempted to incorporate all the essential details of SLNs like various methods of preparation, different models of SLNs, updated characterization methods, in-vivo behavior (Uptake), their applications, route of administration as well as advancements taken place in the field of delivery of biological drugs like gene vector, new adjuvant for vaccines, protein, and peptide with SLNs. Surface modified SLNs hold excellent potential for targeted and controlled drug delivery which is discussed and summarized. Based on the available data, the future success of SLNs is widened because they could be easily fabricated with various functionalities which would display enormous potential for targeting and diagnosing various diseases. This review would help the budding researchers to find out the unexplored areas of SLNs with the present discussion that reframes the potential of SLNs by gathering the various research findings of SLNs in tabular form along with the approved patent technologies of SLNs.
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