Physiological and biochemical regulation of Valeriana jatamansi Jones under water stress.

Understanding the physiological and biochemical regulations in a medicinal plant under stress environments is essential. Here, the effect of water stress such as flooding and water deficit [80% (control), 60%, 40%, 20% field capacity (FC)] conditions on Valeriana jatamansi was studied. Both types of water stresses retarded the plant growth and biomass. Photosynthetic pigments were reduced with maximum reduction under flood stress. Chlorophyll fluorescence study revealed distinct attributes under applied stresses. Better performance index (PI) of flood-grown plants (than 20% and 40% FC) and higher relative fluorescence decrease ratio (Rfd) in 40% FC and flood-grown plants than that of control plants, indicated the adaptation ability of plants under water deficit (40% FC) and flood stress. Reduction in net photosynthetic rate was lesser in flood stress (40.92%) compared to drought stress (73.92% at 20% FC). Accumulation of starch was also decreased (61.1% at 20% FC) under drought stress, while it was increased (24.59%) in flood stress. The effect of water stress was also evident with modulation in H2O2 content and membrane damage. Differential modulation of biosynthesis of secondary metabolites (valtrate, acevaltrate and hydroxyl valerenic acid) and expression of iridoid biosynthetic genes under water stress was also revealed. The present study demonstrated the distinct effect of drought and flood stress on V. jatamansi plants, and drought [20% FC] caused severe loss and more damage than flood stress. Therefore, severe drought should be avoided during cultivation of V. jatamansi and regulated water stress-applications have potential for modulation of biosynthesis of specific secondary metabolites.

Unraveling endophytic diversity in dioecious Siraitia grosvenorii: implications for mogroside production.

Host and tissue-specificity of endophytes are important attributes that limit the endophyte application on multiple crops. Therefore, understanding the endophytic composition of the targeted crop is essential, especially for the dioecious plants where the male and female plants are different. Here, efforts were made to understand the endophytic bacterial composition of the dioecious Siraitia grosvenorii plant using 16S rRNA amplicon sequencing. The present study revealed the association of distinct endophytic bacterial communities with different parts of male and female plants. Roots of male and female plants had a higher bacterial diversity than other parts of plants, and the roots of male plants had more bacterial diversity than the roots of female plants. Endophytes belonging to the phylum Proteobacteria were abundant in all parts of male and female plants except male stems and fruit pulp, where the Firmicutes were most abundant. Class Gammaproteobacteria predominated in both male and female plants, with the genus Acinetobacter as the most dominant and part of the core microbiome of the plant (present in all parts of both, male and female plants). The presence of distinct taxa specific to male and female plants was also identified. Macrococcus, Facklamia, and Propionibacterium were the distinct genera found only in fruit pulp, the edible part of S. grosvenorii. Predictive functional analysis revealed the abundance of enzymes of secondary metabolite (especially mogroside) biosynthesis in the associated endophytic community with predominance in roots. The present study revealed bacterial endophytic communities of male and female S. grosvenorii plants that can be further explored for monk fruit cultivation, mogroside production, and early-stage identification of male and female plants. KEY POINTS: • Male and female Siraitia grosvenorii plants had distinct endophytic communities • The diversity of endophytic communities was specific to different parts of plants • S. grosvenorii-associated endophytes may be valuable for mogroside biosynthesis and monk fruit cultivation.

An Elderly Case of Altered Metabolic Profile Presenting With Respiratory Distress: A Radical Display.

Acute respiratory distress syndrome (ARDS) is a pulmonary pathology that itself can harm and further lead to many other significant hazardous sequelae. Pulmonary vasculature can be distressed by several diseases, but among all the causes, sepsis is one of the main culprits. Its consequences include significant alveolar injury, refractory hypoxemia, ventilation-perfusion mismatch, and destruction of the alveolar-capillary membrane. Dyspnea with diffuse infiltration on a chest X-ray is the most prevalent clinical symptom. Here, we discuss a case of a 62-year-old male patient who presents with ARDS and metabolic anomalies. The patient was treated medically with drug regimens.

Photoredox Minisci-Type Hydroxyfluoroalkylation of Isoquinolines with N-Trifluoroethoxyphthalimide.

A straightforward photocatalytic approach has been demonstrated to incorporate a trifluoroethanol unit onto the isoquinolines. Herein, we report N-trifluoroethoxyphthalimide as a hydroxyfluoroalkyl radical precursor, enabling efficient synthesis of trifluoroethanol-substituted heteroarenes. Radical quenching experiments confirmed the involvement of a free-radical pathway under developed photocatalytic conditions. The DFT calculations confirmed the intramolecular 1,2-HAT reactivity of the O-centered trifluoroethoxy radical (generated from N-trifluoroethoxyphthalimide under photocatalytic condition) to the C-centered trifluoroethanol radical. Fluorescence quenching studies suggested that isoquinoline was responsible for the quenching of Ir-photocatalyst emission. A catalytic cycle involving trifluoroethanol radical reaction with isoquinolines has been proposed.

Plant probiotics - Endophytes pivotal to plant health.

Endophytes as a ubiquitous associate of the plant are considered as a promising candidate for sustainable agriculture. These organisms play a pivotal role in the regulation of the primary and secondary metabolism of their host plant. The direct and long-lasting interaction of endophytes with the host enables them to escape from harsh environmental conditions. Especially, their endophytic nature makes them better candidates over epiphytes and rhizospheric microbes in interaction with plants. Current research findings revealed that the endophytes help plants in making nutrient acquisition from the soil, nitrogen fixation, phosphate availability, phytohormone and antimicrobial production. There is a huge potential for developing novel products like endophytes-based microbial formulations and elicitors to improve plant health, ameliorating stress tolerance in plants and source of therapeutically important secondary metabolites. The present review specifically dealt with attributes such as host-tissue specificity of endophytes, the importance of seed-associated endophytes, endophyte-parasite plant-host plant interaction as well as their applications in plant in-vitro systems and as microbial consortium. In addition, the conserved endophytic microbial communities in different plants are also looked upon possibly to understand the plant-endophytic microbiome on similar lines of the animal-gut microbiome. Primarily, the purpose of this review is to implicate the endophytic flora as probiotics influencing overall plant health and their survival under extreme environmental conditions.

Effect of buerger allen exercise on foot perfusion among patient with diabetes mellitus: A systematic review & meta-analysis.

AIM: Buerger-Allen exercise includes set of activities like elevation, movement and rest of the lower extremities. This systematic review and meta-analysis aimed to assess the effectiveness of BAE on foot perfusion among patient with diabetes mellitus. MATERIAL & METHODS: Five databases were searched for literatures published from inception to October 2020. Cochrane Collaboration Tool for RCTs and ROBINS-I tool for quasi-experimental studies were used for quality assessment. RESULTS: Four RCTs and six quasi-experimental studies were included, and pooled analysis have shown that the BAE was significantly effective in the improvement of ABI scores (MD = 0.14; 95% CI 0.08-0.19; I2 = 30%; p < 0.000). CONCLUSIONS: Studies showed that BAE effectively improves foot perfusion among patients with diabetes mellitus.

Cp*Rh(III)-Catalyzed Regioselective C(sp3)-H Electrophilic Trifluoromethylthiolation of 8-Methylquinolines.

Rh(III)-catalyzed regioselective trifluoromethylthiolation of the unactivated C(sp3)-H bond of 8-methylquinolines with bench-stable electrophilic trifluoromethylthiolating reagent via C(sp3)-H activation is explored. Various substituted 8-methylquinolines provided the products in good yields with high regioselectivity. Current reaction conditions are also applicable for the late-stage functionalization of natural molecule santonin and caffeine-substituted 8-methylquinoline.

Rh(III)-Catalyzed Regioselective C8-Alkylation of Quinoline N-Oxides with Maleimides and Acrylates.

Herein, we disclose the Rh(III)-catalyzed selective C8-alkylation of quinoline N-oxides with maleimides and acrylates. The main features of the reaction include complete C8-selectivity and broad substrate scope with good to excellent yields. The reaction also proceeded well with unprotected maleimide. The applicability of the developed methodology is demonstrated with gram-scale synthesis and post-modification of the alkylated product. Preliminary mechanistic study revealed that the reaction proceeds through a five-membered rhodacycle and involves proto-demetalation step.

Co(III)-Catalyzed C-H Amidation of Nitrogen-Containing Heterocycles with Dioxazolones under Mild Conditions.

A cobalt(III)-catalyzed C-8 selective C-H amidation of quinoline N-oxide using dioxazolone as an amidating reagent under mild conditions is disclosed. The reaction proceeds efficiently with excellent functional group compatibility. The utility of the current method is demonstrated by gram scale synthesis of C-8 amide quinoline N-oxide and by converting this amidated product into functionalized quinolines. Furthermore, the developed catalytic method is also applicable for C-7 amidation of N-pyrimidylindolines and ortho-amidation of benzamides.

Synthesis of a PEGylated Dopamine Ester with Enhanced Antibacterial and Antifungal Activity.

Drug-polymer conjugation is a simple and efficient approach to synthesizing new, effective, and potent antimicrobial agents to counter the problem of microbial resistance. In the present study, a PEGylated dopamine ester (PDE) was synthesized using the PEGylation process and synthesis of PDE was confirmed by Fourier-transform infrared spectroscopy, elemental analysis (CHNS-O), and atomic force microscopy techniques. Later, the antimicrobial activity of PDE was assessed against four strains of bacteria (Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus vulgaris; Gram (-)) and two fungi (Aspergillus niger and Aspergillus fumigatus) by the agar well diffusion method. The minimum inhibitory concentration (MIC) of PDE was also determined by the broth dilution method against bacteria. PDE showed significant zones of inhibition ranged from 21 to 27 mm for bacteria and 16 to 20 mm for fungi under study, which were much higher than those for dopamine hydrochloride. MIC values of PDE showed its potential antimicrobial property.

Immunoprophylactic Potential of a Cocktail of Three Low Molecular Weight Antigens of Leishmania donovani along with Various Adjuvants Against Experimental Visceral leishmaniasis.

BACKGROUND: Currently, there is no vaccine available for any form of leishmaniasis for human use, including visceral leishmaniasis (VL). The treatment relies on drugs associated with severe toxic side effects and increased parasite drug resistance. At present, there is a strong need to develop and implement a successful vaccine against this disease. Therefore, we evaluated immunoprophylactic potential of a cocktail of low molecular weight antigens along with various adjuvants. METHODS: The three antigens (2015, Department of Zoology, Panjab University, Chandigarh), 31kDa, 36 kDa and 51 kDa of L. donovani were used in this study. Inbred BALB/c mice were immunized with 10 µg of cocktail antigens i.e. 31+36+51kDa alone and along with different adjuvants (ALD, saponin, and liposome). Mice were boosted twice at an interval of 2 wk and after last dose; mice were given challenge infection with 107 promastigotes. Mice have sacrificed15 d post immunization and on 30, 60, 90 post-challenge days for evaluation of different parameters. RESULTS: Immunized animals showed reduced parasite load, increased DTH responses and elevated levels of IgG2a antibody. The levels of Th1 cytokines were higher as compared to Th2 cytokines in immunized animals. CONCLUSION: Best results were obtained with cocktail of 31+36+51+liposome and this combination conferred maximum protection.

Studies on the protective efficacy of freeze thawed promastigote antigen of Leishmania donovani along with various adjuvants against visceral leishmaniasis infection in mice.

Visceral leishmaniasis (VL) caused by Leishmania donovani persists as a major public health issue in tropical and subtropical areas of the world. Current treatment of this disease relies on use of drugs. It is doubtful that chemotherapy can alone eradicate the disease, so there is a need for an effective vaccine. Killed antigen candidates remain a good prospect considering their ease of formulation, stability, low cost and safety. To enhance the efficacy of killed vaccines suitable adjuvant and delivery system are needed. Therefore, the current study was conducted to determine the protective efficacy of freeze-thawed L. donovani antigen in combination with different adjuvants against experimental infection of VL. For this, BALB/c mice were immunized thrice at an interval of two weeks. Challenge infection was given two weeks after last immunization. Mice were sacrificed after last immunization and on different post challenge/infection days. Immunized mice showed significant reduction in parasite burden, enhanced DTH responses with increased levels of Th1 cytokines and lower levels of Th2 cytokines, thus indicating the development of a protective Th1 response. Maximum protection was achieved with liposome encapsulated freeze thawed promastigote (FTP) antigen of L. donovani and it was followed by group immunized with FTP+MPL-A, FTP+saponin, FTP+alum and FTP antigen (alone). The present study highlights greater efficacy of freeze thawed promastigote antigen as a potential vaccine candidate along with effective adjuvant formulations against experimental VL infection.

Evaluation of the immunogenicity and protective efficacy of killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis.

Visceral leishmaniasis (VL) caused by Leishmania donovani is a life-threatening disease involving uncontrolled parasitization of vital organs. Drugs to treat leishmaniasis have one or more limitations or insufficiencies in the long run. A safe and efficacious vaccine to control this disease is needed. Killed antigens that could be safer as vaccines have shown limited efficacy in clinical trials. Immunogenic enhancement with appropriate adjuvants may thus be required to elicit protective immunity based on antibodies and effector T-cell functions. Therefore, it is essential to search for adjuvant to enhance the immunogenicity of killed vaccines and to induce protection against leishmaniasis. So, the aim of the present study was to compare the effectiveness of four adjuvants, i.e. alum, saponin, monophosphoryl lipid A, cationic liposome in combination with Killed Leishmania donovani (KLD) antigen against murine VL. Animals were immunized subcutaneously thrice at an interval of 2 weeks with a final volume of 100 µl per dose. Challenge infection was given 2 weeks after last booster. Mice were sacrificed 15 days after last immunization and on 30, 60 and 90 post-infection/challenge days. The protective efficacy of vaccines was revealed by significant reduction in parasite burden and enhanced DTH responses in comparison with the infected controls. Immunized animals also generated significant levels of Th1 cytokines and increased production of IgG2a, thus indicating the generation of a protective Th1 response. All the adjuvants imparted significant protection, but liposomal formulation was most effective followed by KLD + MPL-A, KLD + saponin, KLD + alum and KLD antigen.

Evaluation of the immunoprophylactic potential of a killed vaccine candidate in combination with different adjuvants against murine visceral leishmaniasis.

Despite a large number of field trials, till date no prophylactic antileishmanial vaccine exists for human use. Killed antigen formulations offer the advantage of being safe but they have limited immunogenicity. Recent research has documented that efforts to develop effective Leishmania vaccine have been limited due to the lack of an appropriate adjuvant. Addition of adjuvants to vaccines boosts and directs the immunogenicity of antigens. So, the present study was done to evaluate the effectiveness of four adjuvants i.e. alum, saponin, cationic liposomes and monophosphoryl lipid-A in combination with Autoclaved Leishmania donovani (ALD) antigen against murine visceral leishmaniasis (VL). BALB/c mice were immunized thrice with respective vaccine formulation. Two weeks after last booster, challenge infection was given. Mice were sacrificed 15 days after last immunization and on 30, 60 and 90 post infection/challenge days. A considerable protective efficacy was shown by all vaccine formulations. It was evident from significant reduction in parasite load, profound delayed type hypersensitivity responses (DTH), increased IgG2a titres and high levels of Th1 cytokines (IFN-γ, IL-12) as compared to the infected controls. However, level of protection varied with the type of adjuvant used. Maximum protection was achieved with the use of liposome encapsulated ALD antigen and it was closely followed by group immunized with ALD+MPL-A. Significant results were also obtained with ALD+saponin, ALD+alum and ALD antigen (alone) but the protective efficacy was reduced as compared to other immunized groups. The present study reveals greater efficacy of two vaccine formulations i.e. ALD+liposome and ALD+MPL-A against murine VL.

Protective immunity using MPL-A and autoclaved Leishmania donovani as adjuvants along with a cocktail vaccine in murine model of visceral leishmaniasis.

The current study is an extension of our previous study where we tested the protective efficacy of gp63 and Hsp70 against murine visceral leishmaniasis. The cocktail vaccine was combined with MPL-A and ALD adjuvants and the protection afforded by the three vaccines was compared. Inbred BALB/c mice were immunized twice at an interval of two weeks with the vaccine formulations. Two weeks after the booster, they were challenged with 10(7) promastigotes of Leishmania donovani and sacrificed on 30, 60 and 90 days post infection/challenge. The protective efficacy of vaccines was analyzed by assessment of the hepatic and splenic parasite burden and generation of cellular and humoral immune responses. The immunized animals revealed a significant reduction in parasite burden as compared to the infected controls. These animals also showed heightened DTH response, increased generation of IgG2a, IFN-γ and IL-2 by spleen cells. This was also accompanied by a decrease in the levels of IgG1 and IL-10. Mice immunized with gp63+Hsp70+MPL-A exhibited significantly greater protection in comparison to those immunized with gp63+Hsp70+ALD.

Proapoptotic miltefosine nanovesicles show synergism with paclitaxel: Implications for glioblastoma multiforme therapy.

Hexadecylphosphocholine (HePC) or miltefosine based proapoptotic lipid nanovesicles encapsulating paclitaxel for synergistic anticancer effect of paclitaxel and miltefosine in chemoresistant human glioblastoma multiforme (U-87 MG) overexpressing multidrug resistance 1 (MDR1) gene product P-glycoprotein (P-gp), were developed in this study. The nanovesicles had 100-200nm size and a negative zeta potential (∼-25mV) and optimized for miltefosine content based on their physiochemical properties. With a high encapsulation efficiency of 94%, the nanovesicles showed sustained release of paclitaxel in nasal fluid and triggered release in the cerebrospinal fluid. Synergistic action of paclitaxel and miltefosine was observed with a low IC50 of 162±5nM. The nanovesicle also overcame drug resistance and showed ATP dependent uptake via clathrin mediated pathway in glioblastoma cells. An improved therapeutic efficacy in comparison to Taxol®, the current clinical formulation of paclitaxel was observed. Efficient brain uptake of the nanovesicles upon intranasal administration was observed in vivo and the nanovesicles were also found to be able to cross blood brain barrier. These studies therefore suggest the therapeutic potential of proapoptotic lipid nanovesicles and their feasibility for intranasal administration in the treatment of chemoresistant glioblastoma.

Feed forward artificial neural network: tool for early detection of ovarian cancer.

Pathological changes in an organ or tissue may be reflected in proteomic patterns in serum. The early detection of cancer is crucial for successful treatment. Some cancers affect the concentration of certain molecules in the blood, which allows early diagnosis by analyzing the blood mass spectrum. It is possible that exclusive serum proteomic patterns could be used to differentiate cancer samples from non-cancer ones. Several techniques have been developed for the analysis of mass-spectrum curve, and use them for the detection of prostate, ovarian, breast, bladder, pancreatic, kidney, liver, and colon cancers. In present study, we applied data mining to the diagnosis of ovarian cancer and identified the most informative points of the mass-spectrum curve, then used student t-test and neural networks to determine the differences between the curves of cancer patients and healthy people. Two serum SELDI MS data sets were used in this research to identify serum proteomic patterns that distinguish the serum of ovarian cancer cases from non-cancer controls. Statistical testing and genetic algorithm-based methods are used for feature selection respectively. The results showed that (1) data mining techniques can be successfully applied to ovarian cancer detection with a reasonably high performance; (2) the discriminatory features (proteomic patterns) can be very different from one selection method to another.

Kidney Cancer: Current Progress in Treatment.

Kidney cancer accounts for approximately 2% of all cancers worldwide, with renal cell carcinoma being the most widespread form. Worldwide, the occurrence and mortality rates are rising by 2-3% per decade. Cigarette smoking, obesity, acquired cystic kidney disease and inherited vulnerability are identified risk issues for kidney cancer. Immunotherapy confers a small but significant overall survival benefit in metastatic renal cell carcinoma but only for the minority of patients, i.e. the 20% with good predictive characteristics. Current developments in the molecular biology of renal cell carcinoma have recognized multiple pathways related with the progress of this cancer. Several strategies have been explored targeting these trails, with major clinical benefits shown in early studies. New agents including the small molecule targeted inhibitors like sunitinib, sorafenib and temsirolimus, and the monoclonal antibody bevacizumab have shown anti-tumour activity in randomised clinical trials and have become the standard of care for most patients.