Cannabis, a Miracle Drug with Polyvalent Therapeutic Utility: Preclinical and Clinical-Based Evidence.

Cannabis sativa L. is an annual herbaceous dioecious plant which was first cultivated by agricultural human societies in Asia. Over the period of time, various parts of the plant like leaf, flower, and seed were used for recreational as well as therapeutic purposes. The main chemical components of Cannabis sativa are termed as cannabinoids, among them the key psychoactive constituent is Δ-9-tetrahydrocannabinol and cannabidiol (CBD) as active nonpsychotic constituent. Upon doing extensive literature review, it was found that cannabis has been widely studied for a number of disorders. Very recently, a pure CBD formulation, named Epidiolex, got a green flag from both United States Food and Drug Administration and Drug Enforcement Administration for 2 rare types of epilepsies. This laid a milestone in medical cannabis research. This review intends to give a basic and extensive assessment, from past till present, of the ethnological, plant, chemical, pharmacological, and legal aspects of C. sativa. Further, this review contemplates the evidence the studies obtained of cannabis components on Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, multiple sclerosis, emesis, epilepsy, chronic pain, and cancer as a cytotoxic agent as well as a palliative therapy. The assessment in this study was done by reviewing in extensive details from studies on historical importance, ethnopharmacological aspects, and legal grounds of C. sativa from extensive literature available on the scientific databases, with a vision for elevating further pharmaceutical research to investigate its total potential as a therapeutic agent.

Exploration of Two Pectate Lyases from Caldicellulosiruptor bescii Reveals that the CBM66 Module Has a Crucial Role in Pectic Biomass Degradation.

Pectin deconstruction is the initial step in breaking the recalcitrance of plant biomass by using selected microorganisms that encode pectinolytic enzymes. Pectate lyases that cleave the α-1,4-galacturonosidic linkage of pectin are widely used in industries such as papermaking and fruit softening. However, there are few reports on pectate lyases with good thermostability. Here, two pectate lyases (CbPL3 and CbPL9) from a hyperthermophilic bacterium, Caldicellulosiruptor bescii, belonging to family 3 and family 9 polysaccharide lyases, respectively, were investigated. The biochemical properties of the two CbPLs were shown to be similar under optimized conditions of 80°C to 85°C and pH 8 to 9. However, the degradation products from pectin and polygalacturonic acids (pGAs) were different. A family 66 carbohydrate-binding module (CbCBM66) located in the N terminus of the two CbPLs shares 100% amino acid identity. A CbCBM66-truncated mutant of CbPL9 showed lower activities than the wild type, whereas CbPL3 with a CbCBM66 knockout portion was reported to have enhanced activities, thereby revealing the different effect of CbCBM66. Prediction by the I-TASSER server revealed that CbCBM66 is structurally close to BsCBM66 from Bacillus subtilis; however, the COFACTOR and COACH programs indicated that the substrate-binding sites between CbCBM66 and BsCBM66 are different. Furthermore, a substrate-binding assay indicated that the catalytic domains in the two CbPLs had strong affinities for pectate-related substrates, but CbCBM66 showed a weak interaction with a number of lignocellulosic carbohydrates. Finally, scanning electron microscopy (SEM) analysis and a total reducing sugar assay showed that the two enzymes could improve the saccharification of switchgrass. The two CbPLs are impressive sources for the degradation of plant biomass.IMPORTANCE Thermophilic proteins could be implemented in diverse industrial applications. We sought to characterize two pectate lyases, CbPL3 and CbPL9, from a thermophilic bacterium, Caldicellulosiruptor bescii The two enzymes share a high optimum temperature, a low optimum pH, and good thermostability at the evaluated temperature. A family 66 carbohydrate-binding module (CbCBM66) was identified in the two CbPLs, sharing 100% amino acid identity. The deletion of CbCBM66 dramatically decreased the activity of CbPL9 but increased the activity and thermostability of CbPL3, suggesting different roles of CbCBM66 in the two enzymes. Moreover, the degradation products of the two CbPLs were different. These results revealed that these enzymes could represent potential pectate lyases for applications in the paper and textile industries.

Potential role of adjuvant drugs on efficacy of first line oral antitubercular therapy: Drug repurposing.

Despite the availability of potent antitubercular drugs, tuberculosis (TB) still remains one of the world's leading causes of death. The current antitubercular therapy (ATT) suffers from a drawback of longer duration that imposes a major challenge of patient non compliance and resistance development. The current scenario necessitates alternative strategies with potential to shorten treatment duration that could pave the way for improved clinical outcomes. In recent years, host directed adjunctive therapies have raised considerable attention and emerged as a promising intervention which targets clinically relevant biological pathways in hosts to modulate pathological immune responses. Few of the approved drugs namely statins, metformin, ibuprofen, aspirin, valproic acid, adalimumab, bevacizumab, zileuton and vitamin D3 have shown promising results in clinical outcomes during their preliminary screening in TB patients and can be potentially repurposed as antitubercular drugs. This review highlights clinical and non clinical evidences of some already existing drug and their targets in hosts that could help in shortening treatment duration and reducing bacterial burden at minimal doses.

Growth stage and molybdenum treatment affect cadmium accumulation, antioxidant defence and chlorophyll contents in Cannabis sativa plant.

Cadmium (Cd) uptake and accumulation in plant tissues is affected by physiological stage of a plant and presence of mineral nutrients in soil. We investigate the effect of micronutrient Mo (0.5, 1.0 and 2.0 ppm) on biomass, Cd accumulation, photosynthetic pigments and endogenous phenolics and soluble proline in Cannabis sativa plant grown in 25 and 50 ppm Cd polluted soil. Molybdenum was applied as seed soaking and soil addition treatments. The plants were harvested in two stages i.e. vegetative (6 weeks) and reproductive stages (12 weeks). It was found that seed soaking treatment of 1.0 ppm Mo most significantly increased biomass, Cd accumulation (1.76 ±â€¯0.19 mg Cd/DBM) and phenolics (104.5 ±â€¯4.46 ppm) concentration in the plant tissues. Molybdenum treatments highly increased Cd bio-concentration at reproductive stage as compared to vegetative stage in plants grown in 50 ppm Cd polluted soil. Translocation of Cd from roots into leaves was significantly increased by Mo treatments at reproductive stage as compared to vegetative stage. Strong inter-correlations existed between total phenolics, Cd accumulation, dry biomass and chlorophyll contents of the plant.

Endophyte-mediated synthesis of silver nanoparticles and their biological applications.

Biosynthesis has emerged as a frontier technology for fabrication of functionally diverse nanoparticles that possess tremendous therapeutic implications. Various biological resources have already demonstrated their potential to produce nanoparticles with interesting features. Endophytic microbes live in a symbiotic relationship with plants possessing a unique and versatile reservoir of potentially therapeutic secondary metabolites having the tendency to reduce metallic ions into nanoparticles. Successful biosynthesis of AgNPs using endophytic organisms has already been reported; however, the overall picture about its synthesis and applications is still not clear. In the current article, a comprehensive review of literature was performed for comparing different physical and biological properties of endophytic microbe-derived AgNPs. In addition, the present paper mechanistically explains the synthesis of AgNPs and their diverse pharmacognostic properties. Further studies are encouraged to understand the mechanism of biopharmaceutical effects of these endophyte-mediated NPs.

Aerobic granules cultivated with simultaneous feeding/draw mode and low-strength wastewater: Performance and bacterial community analysis.

Sequence batch reactors (SBR) with simultaneous feeding/draw mode and low-strength wastewater were used for the cultivation of aerobic granules, and analysis of bacterial community diversity were conducted. Results revealed that the ratio of chemical oxygen demand/total nitrogen removal amount for R1 with real wastewater and R2 with synthetic wastewater decreased from 9.9 to 8.7 and, 29.9 to 21.1, respectively, when volumetric exchange ratio (VER) decreased from 90% (stage I) to 50% (stage II), indicating that organic matter in real and low-strength wastewater was fully utilized with lower VER by denitrifying bacteria. Relative abundances of the genus Dechloromonas, Pseudomonas, Bacillus in R1, which are responsible for denitrifying phosphorus removal, were much higher than that in R2, accounting for the high efficiency of nitrogen and phosphorus removal from real wastewater with low influent C/N ratio of 3.6 on average. These results provide useful information for improving wastewater treatment efficiency in the future.

Antimicrobial activity of different solvent extracted samples from the flowers of medicinally important Plumeria obstusa.

The present research work was carried out to investigate the antimicrobial (eight bacteria and one fungus) activities of different solvent (ethanol, petroleum ether, chloroform, ethyl acetate and isobutanol) extracted samples from flowers of P. obstusa by disc diffusion method. Analysis of the data revealed that all the five extracts from flowers of P. obstusa showed different ranges of antimicrobial activities. Petroleum ether fractions showed inhibitory activities against all the nine microbial species except Klebsiella pneumonia. Ethyl acetate and isobutanol fractions showed inhibitory effects against all the tested microbial species except Pseudomonas aeruginosa. Chloroform and ethanol extracts had varying levels of inhibitions against all of the tested microorganisms. The most susceptible gram positive bacterium was Bacillus subtilis which was inhibited by all the five extracts while the most resistant gram positive bacterium was Staphylococcus aureus. Erwinia carotovora was the most susceptible gram negative bacterium while Pseudomonas aeruginosa was highly resistant among the gram negative bacteria.

Screening of Bunium bulbocastanum for antibacterial, antifungal, phytotoxic and haemagglutination activities.

The current study was aimed at screening the Bunium bulbocastanum for its antibacterial, antifungal, phytotoxic and haemagglutination activities.The crude methanolic extract and n-hexane fraction showed significant (89%) and good activity (61%) against Staphylococcus aureus while the CHCl3fraction was moderately active against S.aureus (53%). Moderate activitywas shown by the EtOAc fraction against B. subtilis (44%). This fraction was inactive against P.aerogenosa and S.aureus. The aqueous fraction showed significant activity against B. subtilis (85%), moderate against S.aureus(34 %) and E. coli (33%)and low activity against P.aerogenosa(29%). Our results for antifungal assay indicated that all the test samples were inactive against all the test fungi. The phytotoxic activity of the plant at 1000 and 100 µg/ml was: crude methanolic extract (53.33 and 46.66%), n-hexane (46.66 and 26.66%), CHCl3 (20 and 6.66%), EtOAc (46.66 and 26.66%) and aqueous (40 and 33.33%). All the test samples (crude methanolic extract and fractions) of B. bulbocastanum were unable to agglutinate RBCs of the human blood indicating that this species lack phytolectins.

Neoadjuvant chemo-irradiation in un-resectable carcinoma of rectum.

BACKGROUND: Rectal cancer is one of the most frequent gastrointestinal cancers. Conventionally surgery is the mainstay of treatment, however after surgery alone, local recurrence is high especially in locally advanced rectal cancer, i.e. tethered and fixed rectal cancer. This study was conducted to determine the role of neo-adjuvant (pre-operative) chemoirradiation in locally advanced carcinoma of the rectum to improve resectability, local control and survival. METHODS: Study was conducted in Radiation Oncology department of Shaukat Khanum Memorial Cancer Hospital and Research Center from May 97-Oct 99. Thirteen patients with unresectable/locally advanced adenocarcinoma rectum received neo-adjuvant chemoirradiation, 50 Gray to pelvis by box technique on Cobalt-60 machine with concomitant 5-Flurouracil 500 mg/m2 for first three and last three days followed by abdomino-perineal/low anterior resection. RESULTS: Neo-adjuvant chemoirradiation resulted in resectability rate of 92% and clinical down staging in 11/13 (84%) patients and pathological complete response in 2/13 (15%) patients and a local recurrence rate of 2/13 (15.38%). Non hematological toxicity (diarrhea grade 4--15%, erythema grade 3--23%, dysuria grade 1-2--38%) were main problems observed during neo-adjuvant chemoirradition. CONCLUSION: Concomitant preoperative chemoirradiation for locally advanced rectal cancer is associated with considerable clinical and pathological down staging. Tumor resectability is improved with potential for improved local control and is relatively safe with acceptable morbidity.