A new pipeline to discover antimycotics by inhibiting ergosterol and riboflavin synthesis: the inspirations of Siddha medicine

In this study, we investigated the efficiency of phytochemical constituents from plants mentioned in the Siddha formulations such as Amirthavennai, Kungliavennai, and Mekavarna Kalimbu to inhibit Candidiasis. Enzymatic inhibition of lanosterol 14 α-demethylase and lumazine synthase by the phytochemicals identified from the plants was investigated through molecular docking studies. Grid-based ligand docking with energetics was performed on maestro suite of Schrödinger. Our results reveal that the binding pocket of the currently used drugs (fluconazole and clotrimazole) and the phytochemicals was same. Interestingly, the phytochemicals showed greater binding affinity than standard drugs. It is more likely that these lead compounds can pass through as drug candidates as they are going to be topical application for medication. As these formulations were used by proven efficacy in clinical practice in Siddha medicine system, our study could highlight the possible mechanism of action of phytochemicals present in Siddha formulations.     

Antimicrobial activity of zinc oxide (ZnO) nanoparticle against Klebsiella pneumoniae

Context: Zinc oxide nanoparticles (ZnO Nps) have potential application in piezoelectric nanogenerator and in biotechnology.

Objective: The antibacterial activity of ZnO Nps on Klebsiella pneumoniae (ATCC 70068) and mode of action of ZnO Nps was investigated.

Methods: ZnO Nps was synthesized by a precipitation method and characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) methods. In vitro susceptibility of K. pnumoniae of the ZnO Nps was detected using the disk diffusion method, and the minimum inhibitory concentration (MIC) value was determined using the serial dilution method. The chemical and physical interaction between the cell envelope of K. pneumonia and ZnO Nps was investigated. The effect of ZnO Nps on the cytotoxic activities of K. pneumonia was investigated using a HEp-2 cell line.

Results: The MIC of ZnO Nps was found in 40?µg/ml. The standard growth curve showed that ZnO Nps of 0.75?mM inhibited K. pneumoniae after 4?h. The interaction with outer membrane protein (OMP) and lipoploysacharride (LPS) residues showed modulation in ～66?kDa and ～29?kDa proteins with the use of increasing concentrations of ZnO Nps. The amount of nucleic acid and protein released from the cells increased with the ZnO Nps concentration used. Importantly, the OD of the ZnO Nps-treated cells decreased within 30?min of incubation in the presence of SDS. ZnO Nps-treated K. pneumoniae were five-fold less infectious in the HEp-2 cell line at doses between 0.50 and 0.75?mM.

Discussion: These results suggest the potential antibacterial use of ZnO Nps against K. pneumoniae infections.     

The protelomerase of temperate Escherichia coli phage N15 has cleaving-joining activity

Escherichia coli phage N15 encodes the slightly acidic, 630-residue protein of 72.2 kDa called protelomerase (TelN). TelN is a component of the N15 replication system proposed to be involved in the generation of the linear prophage DNA. This linear DNA molecule has covalently closed ends. The reaction converting circular plasmids into linear molecules was catalyzed in vitro. We demonstrate that the product of telN functions as the protelomerase in the absence of other N15-encoded factors. Purified TelN processes circular and linear plasmid DNA containing the proposed target site telRL to produce linear double-stranded DNA with covalently closed ends. The 56-bp telRL target site consists of a central telO palindrome of 22 bp and two 14-bp flanking sequences comprising inverted repeats. telO is separated from these repeats by 3 bp on each side. The telRL sequence is sufficient for TelN-mediated processing. The ends of the DNA molecules generated in vitro have the same configuration as do those observed in vivo. TelN exerts its activity as cleaving-joining enzyme in a concerted action.     

Therapeutic effect of bone marrow mesenchymal stem cells on cold stress induced changes in the hippocampus of rats

The present study aims to evaluate the effect of bone marrow mesenchymal stem cells on cold stress induced neuronal changes in hippocampal CA1 region of Wistar rats. Bone marrow mesenchymal stem cells were isolated from a 6-week-old Wistar rat. Bone marrow from adult femora and tibia was collected and mesenchymal stem cells were cultured in minimal essential medium containing 10% heat-inactivated fetal bovine serum and were sub-cultured. Passage 3 cells were analyzed by flow cytometry for positive expression of CD44 and CD90 and negative expression of CD45. Once CD44 and CD90 positive expression was achieved, the cells were cultured again to 90% confluence for later experiments. Twenty-four rats aged 8 weeks old were randomly and evenly divided into normal control, cold water swim stress(cold stress), cold stress + PBS(intravenous infusion), and cold stress + bone marrow mesenchymal stem cells(1 × 106; intravenous infusion) groups. The total period of study was 60 days which included 1 month stress period followed by 1 month treatment. Behavioral functional test was performed during the entire study period. After treatment, rats were sacrificed for histological studies. Treatment with bone marrow mesenchymal stem cells significantly increased the number of neuronal cells in hippocampal CA1 region. Adult bone marrow mesenchymal stem cells injected by intravenous administration show potential therapeutic effects in cognitive decline associated with stress-related lesions.     

Pericardiectomy for chronic constrictive pericarditis: risks factors and predictors of survival

Objective

We have performed this study to (1) evaluate the major etiological factors of chronic constrictive pericarditis in this geographical region, (2) evaluate the effect of preoperative optimization, (3) find the best surgical approach, (4) assess the extent of decortication required, (5) evaluate the management of immediate postoperative low cardiac output and (6) determine the predictors of early and long-term survival.

Materials and methods

A retrospective analysis was undertaken in 32 consecutive patients of which 26 were male and 6 female with a mean age of 34.86 years (range 6–64 years), who underwent pericardiectomy for chronic constrictive pericarditis over a period of 5 years (2009–2013), in the affiliated institute in south India.

Results

The perioperative mortality rate was 9.3 %. Tuberculosis was the most common etiology, accounting for 22 cases (68.75 %). Median sternotomy was the most preferred surgical approach, done in 30 patients (93.70 %). Total pericardiectomy was the most preferred surgical procedure, done in 29 patients (90.62 %). Advanced age, atrial fibrillation, concomitant mitral or tricuspid insufficiency, coronary involvement, and low cardiac output state were significant negative predictors of survival. Improved functional status was noted in 24 of the 26 surviving patients (92.30 %) and improvement of NYHA status was observed in 25 of the 26 surviving patients (96.15 %). The actuarial survival in all at 5 years was 84.3 %.

Conclusion

Tuberculosis is the most common etiology for constrictive pericarditis. Median sternotomy is the preferable surgical approach. Total pericardiectomy provides lower perioperative mortality, independent of etiology. Pericardiectomy should be performed early after proper preoperative optimization. Immediate postoperative low cardiac output states should be managed carefully.     

Pancreatic cancer associated with obesity and diabetes: an alternative approach for its targeting

Background

Pancreatic cancer (PC) is among foremost causes of cancer related deaths worldwide due to generic symptoms, lack of effective screening strategies and resistance to chemo- and radiotherapies. The risk factors associated with PC include several metabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus (T2DM). Studies have shown that obesity and T2DM are associated with PC pathogenesis; however, their role in PC initiation and development remains obscure.

Main body

Several biochemical and physiological factors associated with obesity and/or T2DM including adipokines, inflammatory mediators, and altered microbiome are involved in PC progression and metastasis albeit by different molecular mechanisms. Deep understanding of these factors and causal relationship between factors and altered signaling pathways will facilitate deconvolution of disease complexity as well as lead to development of novel therapies. In the present review, we focuses on the interplay between adipocytokines, gut microbiota, adrenomedullin, hyaluronan, vanin and matrix metalloproteinase affected by metabolic alteration and pancreatic tumor progression.

Conclusions

Metabolic diseases, such as obesity and T2DM, contribute PC development through altered metabolic pathways. Delineating key players in oncogenic development in pancreas due to metabolic disorder could be a beneficial strategy to combat cancers associated with metabolic diseases in particular, PC.