N-Alkyl substituted triazenide-bridged homoleptic iron(II) dimers with an exceptionally short Fe-Fe bond.

Dinuclear transition metal complexes with direct metal-metal interactions have the potential to generate unique reactivities and properties. Using asymmetric triazine ligands HN3tBuR (R = Et, iPr, nBu) featuring different alkyl substituents at 1,3-N centers, we report here the first rational synthesis of 'tetragonal lantern' type Fe(II) triazenides [Fe2(N3tBuR)4] [R = Et (1), iPr (2), nBu (3)] having an exceptionally short Fe-Fe distance (2.167-2.174 Å). Unlike the previously reported lantern structures with related amidinate or guanidinate ligands, highly air-sensitive 1-3 show a lower spin ground state, as indicated by Mössbauer, 1H NMR and DFT studies.

Lactate acidosis and simultaneous recruitment of TGF-ß leads to alter plasticity of hypoxic cancer cells in tumor microenvironment.

Lactate acidosis is often observed in the tumor microenvironment (TME) of solid tumors. This is because glucose breaks down quickly via glycolysis, causing lactate acidity. Lactate is harmful to healthy cells, but is a major oncometabolite for solid cancer cells that do not receive sufficient oxygen. As an oncometabolite, it helps tumor cells perform different functions, which helps solid hypoxic tumor cells spread to other parts of the body. Studies have shown that the acidic TME contains VEGF, Matrix metalloproteinases (MMPs), cathepsins, and transforming growth factor-ß (TGF-ß), all of which help spread in direct and indirect ways. Although each cytokine is important in its own manner in the TME, TGF-ß has received much attention for its role in metastatic transformation. Several studies have shown that lactate acidosis can cause TGF-ß expression in solid hypoxic cancers. TGF-ß has also been reported to increase the production of fatty acids, making cells more resistant to treatment. TGF-ß has also been shown to control the expression of VEGF and MMPs, which helps solid hypoxic tumors become more aggressive by helping them spread and create new blood vessels through an unknown process. The role of TGF-ß under physiological conditions has been described previously. In this study, we examined the role of TGF-ß, which is induced by lactate acidosis, in the spread of solid hypoxic cancer cells. We also found that TGF-ß and lactate work together to boost fatty acid production, which helps angiogenesis and invasiveness.

Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival.

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME.

Identification of potential inhibitors of Zika virus targeting NS3 helicase using molecular dynamics simulations and DFT studies.

Despite the various research efforts towards the drug discovery program for Zika virus treatment, no antiviral drugs or vaccines have yet been discovered. The spread of the mosquito vector and ZIKV infection exposure is expected to accelerate globally due to continuing global travel. The NS3-Hel is a non-structural protein part and involved in different functions such as polyprotein processing, genome replication, etc. It makes an NS3-Hel protein an attractive target for designing novel drugs for ZIKV treatment. This investigation identifies the novel, potent ZIKV inhibitors by virtual screening and elucidates the binding pattern using molecular docking and molecular dynamics simulation studies. The molecular dynamics simulation results indicate dynamic stability between protein and ligand complexes, and the structures keep significantly unchanged at the binding site during the simulation period. All inhibitors found within the acceptable range having drug-likeness properties. The synthetic feasibility score suggests that all screened inhibitors can be easily synthesizable. Therefore, possible inhibitors obtained from this study can be considered a potential inhibitor for NS3 Hel, and further, it could be provided as a lead for drug development.

Pituicytoma: Case report of a rare suprasellar tumor.

Pituicytoma is a distinct sellar or supracellar tumor which originates from specialized glial cells of neurohypophyses and infundibulum known as pituicytes. Because of its sellar location patients present with headache, visual disturbance, and endocrine abnormalities. Pituicytoma is difficult to diagnose on neuroimaging as radiological features overlap with other more common tumors of this region. Thus, diagnosis is established by histopathology and immunohistochemistry of resected tumor only. Pituicytomas are composed of bipolar spindle cells arranged as fascicles and are immunoreactive for TTF-1, S100p, and vimentin. These tumors are extremely rare and only around 70 published cases are known in literature. We report a case of suprasellar SOL in a 58-year-old male who presented with headache and gradual visual deterioration in both eyes. He was diagnosed as a case of pituicytoma based on light microscopy findings and immunohistochemical expression of TTF-1, vimentin, S100p, and bcl-2.

Revealing the complexity of protein abundance in chickpea root under drought-stress using a comparative proteomics approach.

Global warming has reached an alarming situation, which led to a dangerous climatic condition. The irregular rainfalls and land degradation are the significant consequences of these climatic changes causing a decrease in crop productivity. The effect of drought and its tolerance mechanism, a comparative roots proteomic analysis of chickpea seedlings grown under hydroponic conditions for three weeks, performed at different time points using 2-Dimensional gel electrophoresis (2-DE). After PD-Quest analysis, 110 differentially expressed spots subjected to MALDI-TOF/TOF and 75 spots identified with a significant score. These identified proteins classified into eight categories based on their functional annotation. Proteins involved in carbon and energy metabolism comprised 23% of total identified proteins include mainly glyceraldehyde-3-phosphate dehydrogenase, malate dehydrogenase, transaldolase, and isocitrate dehydrogenase. Proteins related to stress response (heat-shock protein, CS domain protein, and chitinase 2-like) contributed 16% of total protein spots followed by 13% involved in protein metabolism (adenosine kinase 2, and protein disulfide isomerase). ROS metabolism contributed 13% (glutathione S-transferase, ascorbate peroxidase, and thioredoxin), and 9% for signal transduction (actin-101, and 14-3-3-like protein B). Five percent protein identified for secondary metabolism (cinnamoyl-CoA reductase-1 and chalcone-flavononeisomerase 2) and 7% for nitrogen (N) and amino acid metabolism (glutamine synthetase and homocysteine methyltransferase). The abundance of some proteins validated by using Western blotting and Real-Time-PCR. The detailed information for drought-responsive root protein(s) through comparative proteomics analysis can be utilized in the future for genetic improvement programs to develop drought-tolerant chickpea lines.

Drought tolerant Ochrobactrum sp. inoculation performs multiple roles in maintaining the homeostasis in Zea mays L. subjected to deficit water stress.

Plant growth-promoting rhizobacteria (PGPR) improve plant health under various biotic and abiotic stresses. However, the underlying mechanisms of the protective effects of PGPR in deficit water stress (WS) remain less explored. This study aimed to characterize the role of Ochrobactrum sp. NBRISH6 inoculation on maize (Zea mays "Maharaja") under WS conditions using multiple approaches such as physiological, anatomical, metabolic, and molecular. The effect of NBRISH6 inoculation using maize as a host plant was characterized under greenhouse conditions in deficit water stress. Results from this study demonstrated that NBRISH6 significantly lowered the expression of genes involved in the abscisic acid cycle, deficit water stress-response, osmotic stress, and antioxidant enzyme activity (superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase, and polyphenol oxidase). Phytohormones, i.e. indole acetic acid (IAA) and salicylic acid (SA) levels, intercellular CO2 concentration, metabolites such as simple sugars, amino acids, aliphatic hydrocarbons, and the number of shrunken pith cells modulated in maize roots inoculated with NBRISH6. The NBRISH6 inoculation also improved the plant vegetative properties (root length, 33.80%; shoot length, 20.68%; root dry weight, 39.21%; shoot dry weight, 61.95%), shoot nutrients, xylem cells, root hairs, vapor pressure deficit (75%), intrinsic water-use efficiency (41.67%), photosynthesis rate (83.33%), and total chlorophyll (16.15%) as compared to the respective stress controls. This study provides valuable insights into mechanistic functions of PGPR in WS amelioration and promoting plant physiological response.

Transcriptome and proteome analyses reveal selenium mediated amelioration of arsenic toxicity in rice (Oryza sativa L.).

Arsenic (As), a chronic poison and non-threshold carcinogen, is a food chain contaminant in rice, posing yield losses as well as serious health risks. Selenium (Se), a trace element, is a known antagonist of As toxicity. In present study, RNA seq. and proteome profiling, along with morphological analyses were performed to explore molecular cross-talk involved in Se mediated As stress amelioration. The repair of As induced structural deformities involving disintegration of cell wall and membranes were observed upon Se supplementation. The expression of As transporter genes viz., NIP1;1, NIP2;1, ABCG5, NRAMP1, NRAMP5, TIP2;2 as well as sulfate transporters, SULTR3;1 and SULTR3;6, were higher in As + Se compared to As alone exposure, which resulted in reduced As accumulation and toxicity. The higher expression of regulatory elements like AUX/IAA, WRKY and MYB TFs during As + Se exposure was also observed. The up-regulation of GST, PRX and GRX during As + Se exposure confirmed the amelioration of As induced oxidative stress. The abundance of proteins involved in photosynthesis, energy metabolism, transport, signaling and ROS homeostasis were found higher in As + Se than in As alone exposure. Overall, present study identified Se responsive pathways, genes and proteins involved to cope-up with As toxicity in rice.

Betula utilis extract prolongs life expectancy, protects against amyloid-ß toxicity and reduces Alpha Synuclien in Caenorhabditis elegans via DAF-16 and SKN-1.

Betula utilis (BU), an important medicinal plant that grows in high altitudes of the Himalayan region, has been utilized traditionally due to it's antibacterial, hepatoprotective, and anti-tumor properties. Here, we demonstrated the longevity and amyloid-ß toxicity attenuating activity of B. utilis ethanolic extract (BUE) in Caenorhabditis elegans. Lifespan of the worms was observed under both the standard laboratory and stress (oxidative and thermal) conditions. Effect of BUE was also observed on the attenuation of age-dependent physiological parameters. Further, gene-specific mutants and green fluorescent protein (GFP)-tagged strains were used to investigate the molecular mechanism underlying the beneficial effects mediated by BUE supplementation. Our results showed that BUE (50 µg/ml) extended the mean lifespan of C. elegans by 35.99% and increased its survival under stress conditions. The BUE also reduced the levels of intracellular reactive oxygen species (ROS) by 22.47%. A delayed amyloid-ß induced paralyses was observed in CL4176 transgenic worms. Interestingly, the BUE supplementation was also able to reduce the α-synuclein aggregation in NL5901 transgenic strain. Gene-specific mutant studies suggested that the BUE-mediated lifespan extension was dependent on daf-16, hsf-1, and skn-1 but not on sir-2.1 gene. Furthermore, transgenic reporter gene expression assay showed that BUE treatment enhanced the expression of stress-protective genes such as sod-3 and gst-4. Present findings suggested that ROS scavenging activity, together with multiple longevity mechanisms, were involved in BUE-mediated lifespan extension. Thus, BUE might have potential to increase the lifespan and to attenuate neuro-related disease progression.

Osteoclastic variant of anaplastic thyroid carcinoma: A case report of rare entity.

Anaplastic thyroid carcinoma (ATC) is a rare, highly malignant thyroid tumor with dismal prognosis. Osteoclastic giant cell variant of ATC is extremely rare and is characterized by the presence of a large number of multinucleated giant cells resembling osteoclasts. We report here this unusual variant in a 67-year-old female with a history of long-standing goiter of 13 years duration. Histologically, many multinucleated osteoclast-like giant cells were seen accompanying the malignant spindle cell component. Despite extensive sampling, no evidence of differentiated thyroid malignancy could be elucidated.

In Vivo Toxicity Study of Ethanolic Extracts of Evolvulus alsinoides & Centella asiatica in Swiss Albino Mice.

AIM: We aimed to investigate several parameters after the in vivo acute and sub-acute administration of ethanolic extracts from E. alsinoides & C. asiatica. METHODS: Malignant Ovarian Germ Cell Tumors for in vivo toxicity study guidelines 423 and 407 of Organization for Economic Co-operation and Development (OECD) were followed for acute and sub-acute toxicity assays respectively. For LD50 evaluation, a single dose of ethanolic extracts of Evolvulus alsinoides L. (EEA) and ethanolic extracts of Centella asiatica (ECA) was orally administered to mice at doses of 200, 400, 800, 1600 and 2000 mg/kg. Then the animals were observed for 72 hours. For acute toxicity evaluation, a single dose of both extracts was orally administered to mice at doses of 300, 600, 1200 and 2000 mg/kg and the animals were observed for 14 days. In the sub-acute study, the extracts were orally administered to mice for 28 days at doses of 300, 600, 1200 and 2000 mg/kg. To assess the toxicological effects, animals were closely observed on general behaviour, clinical signs of toxicity, body weight, food and water intake. At the end of the study, it was performed biochemical and hematological evaluations, as well as histopathological analysis from the following organs: brain, heart, liver, and kidney. RESULTS: The oral administration of E. alsinoides and C. asiatica ethanolic extracts, i.e. EEA 300, EEA 600, EEA 1200, EEA 2000, ECA 300, ECA 600, ECA 1200 & ECA 2000 mg/kg doses showed no moral toxicity effect in LD50, acute and sub-acute toxicity parameters. CONCLUSION: In this study, we had found that E. alsinoides & C. asiatica extract at different doses cause no mortality in acute and sub-acute toxicity study. Also, histopathology of kidney, liver, heart, and brain showed no alterations in tissues morphology.

Invasive cutaneous mucormycosis in a preterm neonate presenting as a vesicobullous lesion.

Mucormycosis is a relatively rare fungal infection seen in immunocompromised patients. Very few cases of invasive cutaneous mucormycosis occurring in neonates have been reported in literature. It is an aggressive disease with a mortality rate of around 64% in neonates, so a high index of suspicion is essential for rapid diagnosis and definitive treatment with broad-spectrum antifungals such as Amphotericin B. We present a case of a premature infant born at 25 weeks of gestation who developed vesicobullous lesions all over the body on day 5 of life. Biopsy from the vesicles confirmed the presence of angioinvasive fungal hyphae of mucormycosis which were highlighted on Periodic acid-Schiff and Grocott stain.

Primary Cutaneous B-cell Lymphomas: Case Report of Two Cases.

Primary cutaneous lymphomas are a unique, heterogeneous group of lymphoproliferative disorders which have a primary cutaneous manifestation in the absence of systemic involvement of lymph nodes, bone marrow, or visceral organs at the time of diagnosis. Among the primary cutaneous lymphomas, B-cell lymphoma is much less common and accounts for 20%-25% of cases. Primary cutaneous diffuse large B-cell lymphomas (PCDLBCLs) are aggressive neoplasms with poor prognosis. Early and accurate diagnosis is required as these patients respond well to systemic anthracycline-based chemotherapy (R-CHOP). In this article, we report two cases of PCDLBCL, other which presented with rapidly enlarging skin nodules and were diagnosed based on clinical features, histomorphology, and characteristic immunohistochemical expression. Both the patients were treated with systemic chemotherapy and responded well. During the 6 months' follow-up period, the lesions regressed. The patients are symptom free with no evidence of disease relapse or dissemination to extracutaneous sites.

Targeting H19, an Imprinted Long Non-Coding RNA, in Hepatic Functions and Liver Diseases.

H19 is a long non-coding RNA regulated by genomic imprinting through methylation at the locus between H19 and IGF2. H19 is important in normal liver development, controlling proliferation and impacting genes involved in an important network controlling fetal development. H19 also plays a major role in disease progression, particularly in hepatocellular carcinoma. H19 participates in the epigenetic regulation of many processes impacting diseases, such as activating the miR-200 pathway by histone acetylation to inhibit the epithelial-mesenchymal transition to suppress tumor metastasis. Furthermore, H19's normal regulation is disturbed in diseases, such as hepatocellular carcinoma. In this disease, aberrant epigenetic maintenance results in biallelic expression of IGF2, leading to uncontrolled cellular proliferation. This review aims to further research utilizing H19 for drug discovery and the treatment of liver diseases by focusing on both the epigenetic regulation of H19 and how H19 regulates normal liver functions and diseases, particularly by epigenetic mechanisms.

Asymmetrically substituted triazenes as poor electron donor ligands in the precursor chemistry of iron(ii) for iron-based metallic and intermetallic nanocrystals.

Triazene ligands are introduced, for the first time, in the precursor chemistry for their ability to afford oxygen-free molecular precursors of Fe0 nanoparticles. For this purpose, we synthesized new asymmetric triazene ligands t-BuN[double bond, length as m-dash]N-NHR (R = Et, i-Pr, n-Bu) featuring different alkyl substituents at 1,3-N centers, as well as a symmetric ligand t-BuN[double bond, length as m-dash]N-NHt-Bu and used them to develop novel heteroleptic monomeric FeII triazenide derivatives [Fe(t-BuN3R)2(TMEDA)] (where TMEDA = tetramethylethylenediamine). A range of physico-chemical studies such as FT-IR, TG-DTA, 1H & 13C NMR, mass spectrometry, single crystal X-ray structure analysis, cyclic voltammetry and Mössbauer spectroscopy were used to characterize these newly synthesized ligands and FeII derivatives. One representative derivative [Fe(t-BuN3Et)2(TMEDA)] was evaluated as a precursor for the synthesis of metallic Fe0 and intermetallic Al13Fe4 nanoparticles by the chemical solution deposition method.

Enhanced catalytic activity and near room temperature gas sensing properties of SnO2 nanoclusters@mesoporous Sn(iv) organophosphonate composite.

A simple, facile and one-pot route for preparing SnO2 nanoclusters embedded on a mesoporous Sn(iv) organophosphonate (MSnP) framework is described. Reaction of SnCl4·5H2O with a flexible tris-phosphonic acid, mesityl-1,3,5-tris(methylenephosphonic acid), in the presence of a surfactant under hydrothermal conditions produced the desired nanocomposite, SnO2@MSnP. Analytical, spectroscopic and microscopic studies establish that SnO2@MSnP composite is comprised of SnO2 nanoparticles of an average size of 5 nm evenly and abundantly dispersed over the MSnP framework. The mesoporous metal organophosphonate support significantly augments the catalytic efficacy and vapor sensitivity of SnO2 nanoparticles. The catalytic efficiency of SnO2@MSnP was tested for two acid-catalyzed reactions: deoximation reaction and esterification of fatty acids. SnO2@MSnP exhibits remarkable sensitivity towards ammonia and acetone vapors at near room temperature and under open atmospheric conditions. The present method represents an important step towards preparation of mesoporous metal organophosphonate supported metal oxide nanoclusters and hence offers easy access to functional metal oxide based nanocomposites.

Thoracic psammomatous spinal meningioma with osseous metaplasia: A very rare case report.

Thoracic spinal psammomatous meningioma is a rare subtype of meningioma. Among diverse types of mesenchymal differentiation, osseous metaplasia is found to be still rarer. We are presenting a new case of thoracic psammomatous spinal meningioma with osseous metaplasia in a middle aged female which that gives a sense of cancellous bone in the spinal canal. To conclude, meningiomas with osseous metaplasia are very rare tumors that complicate the surgical removal in certain cases. Ossification, if predicted prior to operation with computed tomography reconstruction, makes planning of removal easier. In our case, maintained cerebrospinal fluid spaces despite hard consistency of tumor made its removal easier once cerebrospinal fluid was drained. We have submitted this article because it is very rare and curable pathology and preoperative diagnosis helps in prevention of neurological injury during its excision.

Elucidation of Complex Nature of PEG Induced Drought-Stress Response in Rice Root Using Comparative Proteomics Approach.

Along with many adaptive strategies, dynamic changes in protein abundance seem to be the common strategy to cope up with abiotic stresses which can be best explored through proteomics. Understanding of drought response is the key to decipher regulatory mechanism of better adaptation. Rice (Oryza sativa L.) proteome represents a phenomenal source of proteins that govern traits of agronomic importance, such as drought tolerance. In this study, a comparison of root cytoplasmic proteome was done for a drought tolerant rice (Heena) cultivar in PEG induced drought conditions. A total of 510 protein spots were observed by PDQuest analysis and 125 differentially regulated spots were subjected for MALDI-TOF MS-MS analysis out of which 102 protein spots identified which further led to identification of 78 proteins with a significant score. These 78 differentially expressed proteins appeared to be involved in different biological pathways. The largest percentage of identified proteins was involved in bioenergy and metabolism (29%) and mainly consists of malate dehydrogenase, succinyl-CoA, putative acetyl-CoA synthetase, and pyruvate dehydrogenase etc. This was followed by proteins related to cell defense and rescue (22%) such as monodehydroascorbate reductase and stress-induced protein sti1, then by protein biogenesis and storage class (21%) e.g. putative thiamine biosynthesis protein, putative beta-alanine synthase, and cysteine synthase. Further, cell signaling (9%) proteins like actin and prolyl endopeptidase, and proteins with miscellaneous function (19%) like Sgt1 and some hypothetical proteins were also represented a large contribution toward drought regulatory mechanism in rice. We propose that protein biogenesis, cell defense, and superior homeostasis may render better drought-adaptation. These findings might expedite the functional determination of the drought-responsive proteins and their prioritization as potential molecular targets for perfect adaptation.

Paenibacillus lentimorbus Inoculation Enhances Tobacco Growth and Extenuates the Virulence of Cucumber mosaic virus.

Previous studies with Paenibacillus lentimorbus B-30488" (hereafter referred as B-30488), a plant growth promoting rhizobacteria (PGPR) isolated from cow's milk, revealed its capabilities to improve plant quality under normal and stress conditions. Present study investigates its potential as a biocontrol agent against an economically important virus, Cucumber mosaic virus (CMV), in Nicotiana tabacum cv. White Burley plants and delineates the physical, biophysical, biochemical and molecular perturbations due to the trilateral interactions of PGPR-host-CMV. Soil inoculation of B-30488 enhanced the plant vigor while significantly decreased the virulence and virus RNA accumulation by ~12 fold (91%) in systemic leaves of CMV infected tobacco plants as compared to the control ones. Histology of these leaves revealed the improved tissue's health and least aging signs in B-30488 inoculated tobacco plants, with or without CMV infection, and showed lesser intercellular spaces between collenchyma cells, reduced amount of xyloglucans and pectins in connecting primary cells, and higher polyphenol accumulation in hypodermis layer extending to collenchyma cells. B-30488 inoculation has favorably maneuvered the essential biophysical (ion leakage and photosynthetic efficiency) and biochemical (sugar, proline, chlorophyll, malondialdehyde, acid phosphatase and alkaline phosphatase) attributes of tobacco plants to positively regulate and release the virus stress. Moreover, activities of defense related enzymes (ascorbate peroxidase, guaiacol peroxidase, superoxide dismutase and catalase) induced due to CMV-infection were ameliorated with inoculation of B-30488, suggesting systemic induced resistance mediated protection against CMV in tobacco. The quantitative RT-PCR analyses of the genes related to normal plant development, stress and pathogenesis also corroborate well with the biochemical data and revealed the regulation (either up or down) of these genes in favor of plant to combat the CMV mediated stress. These improvements led tobacco plant to produce more flowers and seeds with no negative impact on plant health. The present study may advocate the applicability of B-30488 for crop yield improvement in virus infested areas.