Structures of Get3d reveal a distinct architecture associated with the emergence of photosynthesis.

Homologs of the protein Get3 have been identified in all domains yet remain to be fully characterized. In the eukaryotic cytoplasm, Get3 delivers tail-anchored (TA) integral membrane proteins, defined by a single transmembrane helix at their C terminus, to the endoplasmic reticulum. While most eukaryotes have a single Get3 gene, plants are notable for having multiple Get3 paralogs. Get3d is conserved across land plants and photosynthetic bacteria and includes a distinctive C-terminal α-crystallin domain. After tracing the evolutionary origin of Get3d, we solve the Arabidopsis thaliana Get3d crystal structure, identify its localization to the chloroplast, and provide evidence for a role in TA protein binding. The structure is identical to that of a cyanobacterial Get3 homolog, which is further refined here. Distinct features of Get3d include an incomplete active site, a "closed" conformation in the apo-state, and a hydrophobic chamber. Both homologs have ATPase activity and are capable of binding TA proteins, supporting a potential role in TA protein targeting. Get3d is first found with the development of photosynthesis and conserved across 1.2 billion years into the chloroplasts of higher plants across the evolution of photosynthesis suggesting a role in the homeostasis of photosynthetic machinery.

Effect of Chinese medicinal herbal residues compost on tomato and Chinese cabbage plants: Assessment on phytopathogenic effect and nutrients uptake.

Chinese medicinal herbal residues (CMHRs) are known for their antipathogenic properties due to the presence of bioactive compounds. Hence, CMHRs could be used as a potential resource to produce biofertilizer with antipathogenic properties for agricultural applications. In this study, a novel approach was used by utilizing the waste-derived biofertilizer, i.e., CMHRs compost (CMHRC) as a nutrient supplier as well as an organic bioagent against Alternaria solani (A. solani) and Fusarium oxysporum (F. oxysporum) on tomato (Lycopersicon esculentum) and Chinese cabbage (Brassica rapa subsp. Chinensis) plants. The experiments were conducted under greenhouse conditions using locally collected acidic soil wherein 2%, 5% and 10% CMHRC (dry weight) along with 5% food waste compost were used as treatments. In addition, only soil and soil with phytopathogens were used as control treatments. The results suggested that amending the compost into acidic soil significantly increased the pH to a neutral level along with enhanced uptake of nutrients. Among all the treatments, 5% CMHRs compost addition increased the tomato plant biomass production to 4.9 g/pot (dry weight) compared to 2.2 g/pot in control. A similar trend was observed in Chinese cabbage plants and the improved plant biomass production could be attributed to the combined effect of strong nutrient absorption ability by healthy roots and enhanced nutrient supply. At 5% CMHRC application rate, the nitrogen uptake by tomato and Chinese cabbage plants increased by 78% and 62%, respectively, whereas phosphorous uptake increased by 75% and 25%, respectively. The reduction in A. solani by 48% and F. oxysporum by 54% in the post-harvested soil of 5% CMHRC treatment against the control demonstrated the anti-phytopathogenic efficiency of CMHRC compost. Hence, the present study illustrates the beneficiary aspects of utilizing CMHRs to produce biofertilizer with anti-phytopathogenic properties which can be safely used for tomato and Chinese cabbage plant growth.

Intra-rater reliability of goniometry to measure scapular protraction and retraction.

STUDY DESIGN: Observational, descriptive design. BACKGROUND: Despite scapular mobility being essential for the completion of activities of daily living (ADLs), there is currently no established, a reliable goniometric technique to measure scapular protraction and retraction. A proposed method has shown clinically significant inter-rater reliability for a goniometric technique for these measurements. PURPOSE: This observational descriptive study examined the intra-rater reliability of a goniometric technique to assess scapular protraction and retraction among a sample of healthy adults. METHODS: An occupational therapist who is a certified hand therapist (CHT) and an occupational therapy student used goniometry to measure the neutral (resting), protracted, and retracted positions of the right and left scapula for a sample of healthy young adults (n = 54; a total of 108 data points for each measurement). These measurements were compared to analyze intra-rater and inter-rater reliability. RESULTS: For measurements of the scapula in neutral, protraction, and retraction, the standard error of measure (SEM) for repeat measures by the expert and novice raters was < 4.5° and < 3.9° respectively and ICC values ranged from poor to moderate (0.37-0.63). The SEM for measures between evaluators was < 5.0° and the ICC was poor (0.16-0.35). Minimum detectable change (MDC) values as a percentage of the mean (% MDC) ranged between 15.9 and 43.7% for intra-rater reliability and 21.9-52.8% for inter-rater reliability. DISCUSSION: The results of the study were mixed; variance of less than 5° for repeat measures by the same rater and measures between raters suggest clinically acceptable reliability. However, variance as a proportion of available motion (%MDC) demonstrates a broader range both above and below the threshold of 30% suggested for rehabilitation assessments. CONCLUSION: There are few efficient, reliable techniques to measure scapular mobility in clinical practice. The absolute reliability of goniometry to measure scapular protraction and retraction is similar to measurements of other joints. However, additional research and possible refinement of the technique is recommended to further address relative reliability and validity.

PPARD and Interferon Gamma Promote Transformation of Gastric Progenitor Cells and Tumorigenesis in Mice.

BACKGROUND & AIMS: The peroxisome proliferator-activated receptor delta (PPARD) regulates cell metabolism, proliferation, and inflammation and has been associated with gastric and other cancers. Villin-positive epithelial cells are a small population of quiescent gastric progenitor cells. We expressed PPARD from a villin promoter to investigate the role of these cells and PPARD in development of gastric cancer. METHODS: We analyzed gastric tissues from mice that express the Ppard (PPARD1 and PPARD2 mice) from a villin promoter, and mice that did not carry this transgene (controls), by histology and immunohistochemistry. We performed cell lineage-tracing experiments and analyzed the microbiomes, chemokine and cytokine production, and immune cells and transcriptomes of stomachs of these mice. We also performed immunohistochemical analysis of PPARD levels in 2 sets of human gastric tissue microarrays. RESULTS: Thirty-eight percent of PPARD mice developed spontaneous, invasive gastric adenocarcinomas, with severe chronic inflammation. Levels of PPARD were increased in human gastric cancer tissues, compared with nontumor tissues, and associated with gastric cancer stage and grade. We found an inverse correlation between level of PPARD in tumor tissue and patient survival time. Gastric microbiomes from PPARD and control mice did not differ significantly. Lineage-tracing experiments identified villin-expressing gastric progenitor cells (VGPCs) as the origin of gastric tumors in PPARD mice. In these mice, PPARD up-regulated CCL20 and CXCL1, which increased infiltration of the gastric mucosa by immune cells. Immune cell production of inflammatory cytokines promoted chronic gastric inflammation and expansion and transformation of VGPCs, leading to tumorigenesis. We identified a positive-feedback loop between PPARD and interferon gamma signaling that sustained gastric inflammation to induce VGPC transformation and gastric carcinogenesis. CONCLUSIONS: We found PPARD overexpression in VPGCs to result in inflammation, dysplasia, and tumor formation. PPARD and VGPCs might be therapeutic targets for stomach cancer.

Targeted Theranostic Nano Vehicle Endorsed with Self-Destruction and Immunostimulatory Features to Circumvent Drug Resistance and Wipe-Out Tumor Reinitiating Cancer Stem Cells.

The downsides of conventional cancer monotherapies are profound and enormously consequential, as drug-resistant cancer cells and cancer stem cells (CSC) are typically not eliminated. Here, a targeted theranostic nano vehicle (TTNV) is designed using manganese-doped mesoporous silica nanoparticle with an ideal surface area and pore volume for co-loading an optimized ratio of antineoplastic doxorubicin and a drug efflux inhibitor tariquidar. This strategically framed TTNV is chemically conjugated with folic acid and hyaluronic acid as a dual-targeting entity to promote folate receptor (FR) mediated cancer cells and CD44 mediated CSC uptake, respectively. Interestingly, surface-enhanced Raman spectroscopy is exploited to evaluate the molecular changes associated with therapeutic progression. Tumor microenvironment selective biodegradation and immunostimulatory potential of the MSN-Mn core are safeguarded with a chitosan coating which modulates the premature cargo release and accords biocompatibility. The superior antitumor response in FR-positive syngeneic and CSC-rich human xenograft murine models is associated with a tumor-targeted biodistribution, favorable pharmacokinetics, and an appealing bioelimination pattern of the TTNV with no palpable signs of toxicity. This dual drug-loaded nano vehicle offers a feasible approach for efficient cancer therapy by on demand cargo release in order to execute complete wipe-out of tumor reinitiating cancer stem cells.

Society of Toxicologic Pathology Digital Pathology and Image Analysis Special Interest Group Article*: Opinion on the Application of Artificial Intelligence and Machine Learning to Digital Toxicologic Pathology.

Toxicologic pathology is transitioning from analog to digital methods. This transition seems inevitable due to a host of ongoing social and medical technological forces. Of these, artificial intelligence (AI) and in particular machine learning (ML) are globally disruptive, rapidly growing sectors of technology whose impact on the long-established field of histopathology is quickly being realized. The development of increasing numbers of algorithms, peering ever deeper into the histopathological space, has demonstrated to the scientific community that AI pathology platforms are now poised to truly impact the future of precision and personalized medicine. However, as with all great technological advances, there are implementation and adoption challenges. This review aims to define common and relevant AI and ML terminology, describe data generation and interpretation, outline current and potential future business cases, discuss validation and regulatory hurdles, and most importantly, propose how overcoming the challenges of this burgeoning technology may shape toxicologic pathology for years to come, enabling pathologists to contribute even more effectively to answering scientific questions and solving global health issues. [Box: see text].

Stability of live attenuated classical swine fever cell culture vaccine virus in liquid form for developing an oral vaccine.

Classical swine fever (CSF) is an important viral disease of pigs and controlled by vaccination. Unorganised backyard and wild pigs are difficult to vaccinate by needle vaccination. Here we formulated liquid vaccines using an Indian CSF cell culture vaccine virus and four stabilisers and evaluated their stability at 4 °C, 25 °C and 37 °C up to 24 h for use as oral vaccine. The stabilisers were Lactalbumin hydrolysate-Trehalose, Lactalbumin hydrolysate-Trehalose-Gelatin, Lactalbumin hydrolysate-Lactose-Sucrose and Lactalbumin hydrolysate-Sucrose. The liquid vaccines, with or without stabilisers, were stable at 4 °C up to 24 h, whereas, a drop of one log10 titre was observed at 25 °C during the same period. At 37 °C, the virus titre diminished by only one log10 with the Lactalbumin hydrolysate-Trehalose (LT) stabiliser up to 24 h compared to two log10 losses in virus titre with other stabilisers and virus control. We therefore conclude that for developing a CSF oral vaccine, the vaccine virus in liquid form can be used directly during the winter, whereas for developing the oral vaccine for summer, the LT stabiliser would provide maximum stability to the virus to withstand the warm temperature while maintaining adequate therapeutic titre for inducing a protective immune response.

Diagnostic spectro-cytology revealing differential recognition of cervical cancer lesions by label-free surface enhanced Raman fingerprints and chemometrics.

Herein we have stepped-up on a strategic spectroscopic modality by utilizing label free ultrasensitive surface enhanced Raman scattering (SERS) technique to generate a differential spectral fingerprint for the prediction of normal (NRML), high-grade intraepithelial lesion (HSIL) and cervical squamous cell carcinoma (CSCC) from exfoliated cell samples of cervix. Three different approaches i.e. single-cell, cell-pellet and extracted DNA from oncology clinic as confirmed by Pap test and HPV PCR were employed. Gold nanoparticles as the SERS substrate favored the increment of Raman intensity exhibited signature identity for Amide III/Nucleobases and carotenoid/glycogen respectively for establishing the empirical discrimination. Moreover, all the spectral invention was subjected to chemometrics including Support Vector Machine (SVM) which furnished an average diagnostic accuracy of 94%, 74% and 92% of the three grades. Combined SERS read-out and machine learning technique in field trial promises its potential to reduce the incidence in low resource countries.

Characterization of defective interfering (DI) particles of Pestedes petitsruminants vaccine virus Sungri/96 strain-implications in vaccine upscaling.

The present investigation deals with the characterization of defective interfering (DI) particles of Peste-des-petits ruminants (PPR) vaccine Sungri/96 strain generated as a result of high MOI in Vero cells. During the serial 10 passages, infectivity titres drastically reduced from 6.5 to 2.25 log10TCID50/ml at high MOI. Further, attenuation of CPE with high MOI indicated generation of DI particles that resulted in no/slow progression of CPE during the late passages. Monoclonal antibody based cell ELISA indicated normal protein (N & H) packaging in samples with DI activity. At genomic level, inconsistency in amplicon intensity of H gene was observed in RT-PCR, indicating a possible defect of H gene. Further analysis of copy number of PPRV by RT-qPCR indicated intermittent fluctuations of viral genomic RNA copies. The significant decline of viral RNA copies with MOI 3 (314 copies) compared to low MOI (512804 copies), proved that higher DI multiplicities cause more interference with the replication process of the standard virus. Therefore, MOI is critical for manufacturing of vaccines. These investigations will help in upscaling of PPR vaccines in view of ongoing National and Global PPR control and eradication programme.

Haemodynamically Derived Pulmonary Artery Pulsatility Index Predicts Mortality in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary artery (PA) pulsitility index (PAPi) is a novel haemodynamic index shown to predict right ventricular failure in acute inferior myocardial infarction and post left ventricular assist device surgery. We hypothesised that PAPi calculated as [PA systolic pressure - PA diastolic pressure]/right atrial pressure (RAP) would be associated with mortality in the National Institutes of Health Registry for Primary Pulmonary Hypertension (NIH-RPPH). METHODS: The impact of PAPi, the Pulmonary Hypertension Connection (PHC) risk score, right ventricular stroke work, pulmonary artery capacitance (PAC), other haemodynamic indices, and demographic characteristics was evaluated in 272 NIH-RPPH patients using multivariable Cox proportional hazards (CPH) regression and receiver operating characteristic (ROC) analysis. RESULTS: In the 272 patients (median age 37.7+/-15.9years, 63% female), the median PAPi was 5.8 (IQR 3.7-9.2). During 5years of follow-up, 51.8% of the patients died. Survival was markedly lower (32.8% during the first 3years) in PAPi quartile 1 compared with the remaining patients (58.5% over 3years in quartiles 2-4; p<0.0001). The best multivariable CPH survival model included PAPi, the PHC-Risk score, PAC, and body mass index (BMI). In this model, the adjusted hazard ratio for death with increasing PAPi was 0.946 (95% CI 0.905-0.989). The independent ROC areas for 5-year survival based on bivariable logistic regression for PAPi, BMI, PHC Risk, and PAC were 0.63, 0.62, 0.64, and 0.65, respectively (p<0.01). The ROC area for 5-year survival for the multivariable logistic model with all four covariates was 0.77 (p<0.0001). CONCLUSIONS: Pulmonary artery pulsatility index was independently associated with survival in PAH, highlighting the utility of PAPi in combination with other key measures for risk stratification in this population.

Increased Pulmonary-Systemic Pulse Pressure Ratio Is Associated With Increased Mortality in Group 1 Pulmonary Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterised by remodelling of the pulmonary vasculature leading to right ventricular (RV) failure. The failing RV, through interventricular uncoupling, deleteriously impacts the left ventricle and overall cardiac efficiency. We hypothesised that the ratio of the pulmonary artery pulse pressure to the systemic pulse pressure ("pulmonary-systemic pulse pressure ratio", or PS-PPR) would be associated with mortality in PAH. METHODS: We conducted a retrospective analysis of 262 patients in the National Institute of Health Primary Pulmonary Hypertension Registry (NIH-PPH). We evaluated the association between the PS-PPR and mortality after adjustment for the Pulmonary Hypertension Connection (PHC) risk equation. RESULTS: Among 262 patients (mean age 37.5±15.8years, 62.2% female), median PS-PPR was 1.04 (IQR 0.79-1.30). In the Cox proportional hazards regression model, each one unit increase in the PS-PPR was associated with more than a two-fold increase in mortality during follow-up (HR 2.06, 95% CI 1.40-3.02, p=0.0002), and this association of PS-PPR with mortality remained significant in the multivariable Cox model adjusted for the PHC risk equation, mean pulmonary artery pressure, and body mass index (BMI) (adjusted HR 1.81, 95% CI 1.13-2.88, p=0.01). Furthermore, PS-PPR in the upper quartile (>1.30) versus quartiles 1-3 was associated with a 68% increase in mortality after adjustment for these same covariates (adjusted HR 1.68, 95% CI 1.13-2.50, p=0.01). CONCLUSIONS: Pulmonary-systemic pulse pressure ratio, a marker of biventricular efficiency, is associated with survival in PAH even after adjustment for the PHC risk equation. Further studies are needed on the wider applications of PS-PPR in PAH patients.

Chloroform as a carbon monoxide source in palladium-catalyzed synthesis of 2-amidoimidazo[1,2-a]pyridines.

A palladium-catalyzed aminocarbonylation strategy exploiting chloroform as a CO source has been developed for the synthesis of biologically potent 2-amidoimidazopyridine scaffolds. The aminocarbonylation reaction was found to be general with a range of amines and substituted imidazopyridines. Preliminary biological evaluation of cytotoxicity on selected examples provides scope for future investigations.

Right atrial to left atrial volume index ratio is associated with increased mortality in patients with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance leading to right heart failure. Elevated right atrial (RA) pressure reflects right ventricular (RV) pressure overload and is an established risk factor for mortality in PH. We hypothesized that PH patients with an increased ratio of RA to LA volume index (RAVI/LAVI), would have increased mortality. METHODS: We evaluated the association of RAVI/LAVI with mortality in 124 patients seen at a single academic center's PH clinic after adjusting for the REVEAL risk score, an established risk score in PH. LA and RA volume indices were measured in the four-and two-chamber views by two independent researchers. Multivariable logistic regression was used to model the independent association of RAVI/LAVI with survival. RESULTS: Among 124 patients (mean age 62 ± 12.7 years, 68.6% female), each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.91, 95% CI: 1.20-3.04). In a multivariable logistic regression, each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.73, 95% CI: 1.003-2.998). Furthermore, RAVI/LAVI in the highest quartile (>1.42) was significantly associated with elevated right atrial pressure (RAP) to pulmonary artery wedge pressure ratio (RAP/PAWP) (0.76 ± 0.41, P = 0.02) compared with the lowest quartile (<0.77), suggesting an interaction between invasive hemodynamic data, atrial structural changes, and mortality in PH. CONCLUSIONS: Increased RAVI/LAVI in PH is associated with decreased survival and accounts for atrial structural remodeling related to invasive hemodynamics. These findings support further study of this index in predicting outcomes in PH.

Heritability and genetic basis of protein level variation in an outbred population.

The genetic basis of heritable traits has been studied for decades. Although recent mapping efforts have elucidated genetic determinants of transcript levels, mapping of protein abundance has lagged. Here, we analyze levels of 4084 GFP-tagged yeast proteins in the progeny of a cross between a laboratory and a wild strain using flow cytometry and high-content microscopy. The genotype of trans variants contributed little to protein level variation between individual cells but explained >50% of the variance in the population's average protein abundance for half of the GFP fusions tested. To map trans-acting factors responsible, we performed flow sorting and bulk segregant analysis of 25 proteins, finding a median of five protein quantitative trait loci (pQTLs) per GFP fusion. Further, we find that cis-acting variants predominate; the genotype of a gene and its surrounding region had a large effect on protein level six times more frequently than the rest of the genome combined. We present evidence for both shared and independent genetic control of transcript and protein abundance: More than half of the expression QTLs (eQTLs) contribute to changes in protein levels of regulated genes, but several pQTLs do not affect their cognate transcript levels. Allele replacements of genes known to underlie trans eQTL hotspots confirmed the correlation of effects on mRNA and protein levels. This study represents the first genome-scale measurement of genetic contribution to protein levels in single cells and populations, identifies more than a hundred trans pQTLs, and validates the propagation of effects associated with transcript variation to protein abundance.

Emergence of Gold-Mesoporous Silica Hybrid Nanotheranostics: Dox-Encoded, Folate Targeted Chemotherapy with Modulation of SERS Fingerprinting for Apoptosis Toward Tumor Eradication.

Strategically fabricated theranostic nanocarrier delivery system is an unmet need in personalized medicine. Herein, this study reports a versatile folate receptor (FR) targeted nanoenvelope delivery system (TNEDS) fabricated with gold core silica shell followed by chitosan-folic acid conjugate surface functionalization by for precise loading of doxorubicin (Dox), resembled as Au@SiO2 -Dox-CS-FA. TNEDS possesses up to 90% Dox loading efficiency and internalized through endocytosis pathway leading to pH and redox-sensitive release kinetics. The superior FR-targeted cytotoxicity is evaluated by the nanocarrier in comparison with US Food and Drug Administration (FDA)-approved liposomal Dox conjugate, Lipodox. Moreover, TNEDS exhibits theranostic features through caspase-mediated apoptosis and envisages high surface plasmon resonance enabling the nanoconstruct as a promising surface enhanced Raman scattering (SERS) nanotag. Minuscule changes in the biochemical components inside cells exerted by the TNEDS along with the Dox release are evaluated explicitly in a time-dependent fashion using bimodal SERS/fluorescence nanoprobe. Finally, TNEDS displays superior antitumor response in FR-positive ascites as well as solid tumor syngraft mouse models. Therefore, this futuristic TNEDS is expected to be a potential alternative as a clinically relevant theranostic nanomedicine to effectively combat neoplasia.

Computational and mechanistic studies on the effect of galactoxyloglucan: Imatinib nanoconjugate in imatinib resistant K562 cells.

Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects. This study involved in the synthesis of PST-Imatinib nanoconjugates with appreciable drug payload and excellent cytotoxicity against drug-resistant chronic myelogenous leukemia cell line (K562) in comparison with free drug. The use of bioinformatics tool revealed better binding affinity for the drug-polysaccharide complex than the drug alone with three proteins: 3QX3 (Topoisomerase), 1M17 (EGFR tyrosine kinase domain), and 3QRJ (ABL1 kinase domain). Assessment of the biochemical, hematological, and histopathological parameters in mice upheld the security and adequacy of the nanoconjugate compared to free drug. Although perspective investigations are warranted, in a condition like drug resistance in leukemia, this nanoconjugate would display a productive approach in cancer therapeutics.

A Ratiometric Near-Infrared Fluorogen for the Real Time Visualization of Intracellular Redox Status during Apoptosis.

Direct monitoring of apoptotic progression is a major step forward for the early assessment of therapeutic efficacy of certain treatments and the accurate evaluation of the spread of a disease. Here, the regulatory role of glutathione (GSH) is explored as a potential biomarker for tracking apoptosis. For this purpose, a near- infrared (NIR) squaraine dye is introduced that is capable of sensing GSH in a ratiometric manner by switching its emission from NIR (690 nm) to visible region (560 nm). The favorable biocompatible attributes of the probe facilitated the real-time monitoring of apoptotic process in line with the conventional apoptotic assay. Furthermore, the robust nature of the probe was utilized for the quantitative estimation of GSH during different stages of apoptosis. Through this study, an easy and reliable method of assaying apoptosis is demonstrated, which can provide valuable insights in translational clinical research.

Plasmonically Enhanced Galactoxyloglucan Endowed Gold Nanoparticles Exposed Tumor Targeting Biodistribution Envisaged in a Surface-Enhanced Raman Scattering Platform.

Biopolymer-capped gold nanoparticles (AuNPs) were perceived for tracing biodistribution in a solid tumor mice through surface-enhanced Raman scattering (SERS) fingerprinting. In this strategy, a robust and ecofriendly green chemistry approach was adopted to construct galactoxyloglucan (PST001) endowed AuNPs (PST-GNPs) with cancer-cell-selective toxic nature and excellent biocompatibility. Plasmonically enhanced light-scattering properties facilitated PST-GNPs to be a superior SERS substrate with high Raman signal enhancement. In this context, PST-GNPs were scrutinized for the noninvasive label-free SERS live-cell spectral imaging to evaluate the fingerprint molecular details of cellular processes. Consequently, the inherent SERS feature of PST-GNPs enabled us to investigate the dynamic and complex nature with NP biodistrubution in tumor-bearing mice on a SERS platform that illustrated the tumor targeting nature. Henceforth, the present findings emphasized a futuristic clinically relevant scenario for tracing the in vivo NP dissemination in a label-free fashion for providing vital biochemical details on a molecular level.

Bisindole-oxadiazole hybrids, T3P® -mediated synthesis, and appraisal of their apoptotic, antimetastatic, and computational Bcl-2 binding potential.

In the pursuit of novel anticancer leads, new bisindole-oxadiazoles were synthesized using propyl phosphonic anhydride as a mild and efficient reagent. The molecule, 3-[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indole (3a) exhibited selective cytotoxicity to MCF-7 cells with a cell cycle arrest in the G1 phase. The mechanism of cytotoxicity of 3a involved caspase-2-dependent apoptotic pathway with characteristic apoptotic morphological alterations as observed in acridine orange/ethidium bromide and Hoechst staining. The wound healing migratory assay exhibited an intense impairment in the motility of MCF-7 cells on incubation with 3a. Docking simulations with anti-apoptotic protein Bcl-2, which is also involved in cancer metastasis displayed good affinity and high binding energy of 3a into the well characterized BH3 binding site. The positive correlation between the Bcl-2 binding studies and the results of in vitro investigations exemplifies compound 3a as a lead molecule exhibiting MCF-7 differential cytotoxicity via apoptotic mode of cell death in addition to its anti-metastatic activity.

Cardiac Troponin T and creatine kinase MB fraction levels among patients with acute ischemic stroke in Nigeria.

BACKGROUND: Stroke has been a global burden, with increasing morbidity and mortality. Serum cardiac troponin t (cTnT) and creatine kinase (CK-MB) fraction are reported to be elevated in patients admitted with acute ischaemic stroke and high level of these biomarkers indicated more severe stroke and neurologic deficit in some of the patients. OBJECTIVE: To evaluate the serum levels cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in patients with acute ischaemic stroke and relate the analytes to severity of stroke. METHOD: Patients with clinical diagnosis of ischaemic stroke diagnosed, confirmed by brain Computerized Tomography scan and equal number of apparently healthy age and sex-matched were recruited. Serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) were analysed using ELISA method and Stroke severity was determined using National Institute of Health Stroke Score (NIHSS). RESULTS: Mean serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in stroke patients were found to be higher than age sex matched control (p<0.05). NIHS Score of 12.2 ± 5.43 and 9.78 ± 3.97 were observed in Patients with elevated and normal cTnT respectively (p=0.009) while NIHS Score were similar in patients with elevated and normal CK-MB (p = 0.772). CONCLUSION: The mean values of serum cTnT and CK-MB were higher in acute ischaemic stroke patients compared to controls. Serum cardiac Troponin t level may be a significant biomarker of the severity of stroke.