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Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives. Assessing progress towards designing reliable wearable biosensors reveals the challenges remaining before the promise of clinical translation can be realized.

Natural antioxidants present in several medicinal plants are responsible for inhibiting the harmful effects of oxidative stress. These plants contain polyphenols and flavonoids that act as free radical scavengers and reduce oxidative stress and may be an alternative remedy to cure various harmful human diseases. This study aims to quantify the total phenolic and flavonoid contents (TPC and TFC) and antioxidant properties of methanol extracts of fruits, seeds, and bark of an important medicinal and aromatic plant, Zanthoxylum armatum collected from wild and cultivated populations in Nepal. TPC was determined by Folin–Ciocalteu colorimetric method using gallic acid as standard, and various concentrations of the extract solutions were measured at 760 nm. TFC was calculated by aluminum chloride colorimetric assay. Quercetin was used as standard, and the absorbance was measured at 510 nm. The antioxidant potential of the different extracts was estimated by DPPH free radical scavenging assay, and the absorbance was measured at 517 nm. The highest TPC value was 226.3 ± 1.14 mg GAE/g in wild fruits, and the lowest was 137.72 ± 4.21 mg GAE/g in cultivated seeds. Similarly, the highest TFC value was 135.17 ± 2.02 mg QE/g in cultivated fruits, and the lowest was 76.58 ± 4.18 mg QE/g in cultivated seeds. The extracts showed variable antioxidant properties. The fruits exhibited excellent antioxidant properties with IC50 values of 40.62 μg/mL and 45.62 μg/mL for cultivated and wild fruits, respectively. Similarly, the IC50 values of the bark were 63.39 μg/mL and 67.82 μg/mL, respectively, for cultivated and wild samples. And the least antioxidant capacity was shown by the seeds extract with IC50 values of 86.75 μg/mL and 94.49 μg/mL for wild and cultivated seeds, respectively. The IC50 value of the standard ascorbic acid was 36.22 μg/mL. Different extracts of Z. armatum contain considerable amount of phenols and flavonoids, including antioxidant properties, suggesting the potential use of this species in pharmacy and phytotherapy as a source of natural antioxidants.

Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal failure worldwide. lncRNAs are demonstrated to improve the DN by changing the expression of miRNAs. This study was aimed to investigate the effect of lncRNA GAS5/miR-452-5p on the inflammation, oxidative stress and pyroptosis of high-glucose-induced renal tubular cells. Methods: HK-2 cells were induced by HG to simulate DN cells. RT-qPCR analysis confirmed the transfection effects and detected the expression of GAS5, NLRP3, caspase1, IL-1[beta], procaspase1, pro-IL-1[beta], GSDMD-N and miR-452-5p. Western blot analysis determined the protein expression of NLRP3, caspase1, IL-1[beta], pro-caspase1, pro-IL-1[beta] and GSDMD-N. The expression of GSDMD-N was also verified by immunofluorescence. The levels of TNF-[alpha], IL-6, MCP-1, ROS, MDA and SOD were measured by commercial assay kits, respectively. Dual-luciferase reporter assay indicated that GAS5 could combine with miR-452-5p. Results: GAS5 expression was decreased in HG-induced HK-2 cells. GAS5 overexpression could decrease the levels of TNF-[alpha], IL-6, MCP-1, ROS and MDA and increase the levels of SOD. Moreover, GAS5 overexpression suppressed the expression of NLRP3, caspase1, IL-1[beta] and GSDMD-N, and the results of immunofluorescence verified the above results. miR-452-5p interference could cause the same changes as GAS5 overexpression for HG-induced HK-2 cells, and GAS5 inhibition could reverse the effect of miR-452-5p interference. Conclusion: GAS5 overexpression inhibited the inflammation, oxidative stress and pyroptosis of HG-induced renal tubular cells by downregulating the expression of miR-452-5p. Keywords: lncRNA GAS5, miR-452-5p, oxidative stress, pyroptosis, high glucose, renal tubular cells

Neuroinflammation has recently emerged as a critical risk factor in the pathophysiology of depression. However, the underlying molecular mechanisms and the development of novel therapeutic strategies as means to target these inflammatory pathways for use in the treatment of depression remain unresolved. In the present study, we aimed to investigate the molecular events of neuroinflammation as related to its induction of depression-like behaviors. Chronic unpredictable mild stress (CUMS) or lipopolysaccharide (LPS) was used to induce depression-like behaviors in rats. The inflammatory factors and related proteins were verified by RT-PCR, immunoblotting, and immunofluorescence assay. In vivo intracerebral injection of adenovirus-associated virus (AAV) in rats was used to overexpress or block the function of the [beta] form of the calcium/calmodulin-dependent protein kinase type II ([beta]CaMKII). In vivo intracerebroventricular injection of SB203580 was used to block p38 mitogen-activated protein kinase (MAPK). Finally, the prostaglandin E2 (PGE2) concentration was verified by using enzyme-linked assay kit. The expression of cyclo-oxygenase (COX)-2, which is responsible for production of the pro-inflammatory factor PGE2 and thus glial activation, was increased in the CA1 hippocampus in a rat model of depression. Further, the [beta]CaMKII in CA1 was significantly upregulated in depressed rats, while antidepressant treatment downregulated this kinase. Overexpression of [beta]CaMKII via infusion of a constructed AAV-[beta]CaMKII into the CA1 region resulted in phosphorylation of the p38 MAPK and the activating transcription factor 2 (ATF2). These effects were accompanied by an enhanced activity of the COX-2/PGE2 pathway and effectively induced core symptoms of depression. Conversely, knockdown of [beta]CaMKII within the CA1 region reversed these inflammation-related biochemical parameters and significantly rescued depression symptoms. These results demonstrate that [beta]CaMKII can act as a critical regulator in depression via activating neuroinflammatory pathways within the CA1 region. Moreover, this study provides new perspectives on molecular targets and drug therapies for future investigation in the treatment of depression.

Background Bone marrow-derived mesenchymal stem cell (BMSC) transplantation is one of the new therapeutic strategies for treating ischemic brain and heart tissues. However, the poor survival rate of transplanted BMSCs in ischemic tissue, due to high levels of reactive oxygen species (ROS), limits the therapeutic efficacy of this approach. Considering that BMSC survival may greatly enhance the effectiveness of transplantation therapy, development of effective therapeutics capable of mitigating oxidative stress-induced BMSC apoptosis is an important unmet clinical need. Methods BMSCs were isolated from the 4-week-old male Sprague Dawley rats by whole bone marrow adherent culturing, and the characteristics were verified by morphology, immunophenotype, adipogenic, and osteogenic differentiation potential. BMSCs were pretreated with artemisinin, and H 2 O 2 was used to induce apoptosis. Cell viability was detected by MTT, FACS, LDH, and Hoechst 33342 staining assays. Mitochondrial membrane potential (ΔΨm) was measured by JC-1 assay. The apoptosis was analyzed by Annexin V-FITC/PI and Caspase 3 Activity Assay kits. ROS level was evaluated by using CellROX® Deep Red Reagent. SOD, CAT, and GPx enzymatic activities were assessed separately using Cu/Zn-SOD and Mn-SOD Assay Kit with WST-8, Catalase Assay Kit, and Total Glutathione Peroxidase Assay Kit. The effects of artemisinin on protein expression of BMSCs including p-Erk1/2, t-Erk1/2, p-c-Raf, p-p90 rsk , p-CREB, BCL-2, Bax, p-Akt, t-Akt, β-actin, and GAPDH were measured by western blotting. Results We characterized for the first time the protective effect of artemisinin, an anti-malaria drug, using oxidative stress-induced apoptosis in vitro, in rat BMSC cultures. We found that artemisinin, at clinically relevant concentrations, improved BMSC survival by reduction of ROS production, increase of antioxidant enzyme activities including SOD, CAT, and GPx, in correlation with decreased Caspase 3 activation, lactate dehydrogenase (LDH) release and apoptosis, all induced by H 2 O 2 . Artemisinin significantly increased extracellular-signal-regulated kinase 1/2 (Erk1/2) phosphorylation, in a concentration- and time-dependent manner. PD98059, the specific inhibitor of the Erk1/2 pathway, blocked Erk1/2 phosphorylation and artemisinin protection. Similarly, decreased expression of Erk1/2 by siRNA attenuated the protective effect of artemisinin. Additionally, when the upstream activator KRAS was knocked down by siRNA, the protective effect of artemisinin was also blocked. These data strongly indicated the involvement of the Erk1/2 pathway. Consistent with this hypothesis, artemisinin increased the phosphorylation of Erk1/2 upstream kinases proto-oncogene c-RAF serine/threonine-protein kinase (c-Raf) and of Erk1/2 downstream targets p90 ribosomal s6 kinase (p90 rsk ) and cAMP response element binding protein (CREB). In addition, we found that the expression of anti-apoptotic protein B cell lymphoma 2 protein (BcL-2) was also upregulated by artemisinin. Conclusion These studies demonstrate the proof of concept of artemisinin therapeutic potential to improve survival in vitro of BMSCs exposed to ROS-induced apoptosis and suggest that artemisinin-mediated protection occurs via the activation of c-Raf-Erk1/2-p90 rsk -CREB signaling pathway.

Background Chemical reduction has become an accessible and useful alternative to obtain silver nanoparticles (AgNPs). However, its toxicity capacity depends on multiple variables that generate differences in the ability to inhibit the growth of microorganisms. Thus, optimazing parameters for the synthesis of AgNPs can increase its antimicrobial capacity by improving its physical-chemical properties. Methods In this study a Face Centered Central Composite Design (FCCCD) was carried out with four parameters: A g N O 3 concentration, sodium citrate (TSC) concentration, N a B H 4 concentration and the pH of the reaction with the objective of inhibit the growth of microorganisms. The response variables were the average size of AgNPs, the peak with the greatest intensity in the size distribution, the polydispersity of the nanoparticle size and the yield of the process. AgNPs obtained from the optimization were characterized physically and chemically. The antimicrobial activity of optimized AgNPs was evaluated against Staphylococcus aureus , Escherichia coli , Escherichia coli AmpC resistant, and Candida albicans and compared with AgNPs before optimization. In addition, the cytotoxicity of the optimized AgNPs was evaluated by the colorimetric assay MTT (3- (4,5- Dimethylthiazol- 2- yl)- 2, 5 - Diphenyltetrazolium Bromide). Results It was found that the four factors studied were significant for the response variables, and a significant model (p < 0.05) was obtained for each variable. The optimal conditions were 8 for pH and 0.01 M, 0.0 6M, 0.01 M for the concentration of TSC, A g N O 3 , and N a B H 4 , respectively. Optimized AgNPs spherical and hemispherical were obtained, and 67.66% of it had a diameter less than 10.30 nm. A minimum bactericidal concentration (MBC) and minimum fungicidal Concentration (MFC) of optimized AgNPs was found against Staphylococcus aureus , Escherichia coli , Escherichia coli AmpC resistant, and Candida albicans at 19.89, 9.94, 9.94, 2.08 μ g/mL, respectively. Furthermore, the lethal concentration 50 ( L C 50 ) of optimized AgNPs was found on 19.11 μ g/mL and 19.60 μ g/mL to Vero and NiH3T3 cells, respectively. Conclusions It was found that the factors studied were significant for the variable responses and the optimization process used was effective to improve the antimicrobial activity of the AgNPs.

Myocardial injury is one of the main symptoms of sepsis. However, the mechanisms underlying sepsis-induced myocardial dysfunction remain unclear. In the present study, the concentration of cardiac troponin T (CTnT) in serum was measured using an enzyme-linked immunosorbent assay kit. The levels of interleukin (IL)-1β and IL-18 were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and the level of malondialdehyde (MDA) was determined using a corresponding kit. Myocardial pathology was analyzed via hematoxylin and eosin staining. RT-qPCR analysis and western blotting and/or immunohistochemistry were used to quantify the expression levels of thioredoxin-interacting protein (TNXIP), NOD-like receptor pyrin domain containing 3 (NLRP3), cleaved caspase-1, caspase-1, catalase and manganese-superoxide dismutase (MnSOD). The viability of cells was determined using a cell counting kit-8. Apoptosis and reactive oxygen species (ROS) were examined using flow cytometry. Models of sepsis-induced myocardial injury were successfully established; evidence included increases in the levels of CTnT, IL-1β, IL-18 and MDA and myocardial tissue damage in vivo, and decreased cell viability and improvements in IL-1β and IL-18 in vitro. The levels of TXNIP, NLRP3 and cleaved caspase-1 were upregulated in the sepsis models. Small interfering RNA targeting TNXNIP (siTXNIP) increased cell viability, reduced the apoptotic rate and attenuated the release of IL-1β and IL-18. The levels of TXNIP, NLRP3 and cleaved caspase-1 and production of ROS were suppressed by siTXNIP, accompanied by increases in catalase and MnSOD. TXNIP/NLRP3 serves an important role in the development of sepsis-induced myocardial damage.

Reduction of tetrazolium salts to colored formazan products by metabolically active cells is widely used for assessment of cell viability. Among the tetrazolium compounds most commonly used is MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. Numerous studies about sites and mechanisms of cellular reduction of MTT, performed in mammalian cell cultures, have identified various parameters that affect formazan production and can lead to overestimation/underestimation of viable cells or effects of treatment. Irrespective of lack of such data for prokaryotic cells, the MTT assay is commonly used for microbiological studies, which often leads to contradictory results or misinterpretation of data. The aim of this study was to investigate how components of growth media and conditions of growth, affect formazan formation by microbial cells. Results showed that MTT reduction depended on the amino acid composition of the medium. Several amino acids potentiated formazan production by Gram-positive and Gram-negative bacteria, with histidine having the strongest effect. Results of this study demonstrate that data obtained with the MTT test should be interpreted with caution, particularly when different growth media are used or treatments affect metabolic pathways, and that evaluation of the reliability of the MTT assay under specific conditions should be performed, to avoid erroneous results. Performing the assay with cells suspend in glucose-supplemented buffer would eliminate the effects of metabolites and will limit cell division during incubation with MTT. Another critical element to be considered is the choice of a proper solvent for dissolution of formazan crystals.

Thiazole and thiosemicarbazone derivatives are known to have potential anticancer activity with a mechanism of action related to inhibition of matrix metallo-proteinases, kinases and anti-apoptotic BCL2 family proteins. A novel three series of 5-(1-(2-(thiazol-2-yl)hydrazono)ethyl)thiazole derivatives were prepared in a one-pot three-component reaction using 2-(2-benzylidene hydrazinyl)-4-methylthiazole as a starting precursor. MS, IR, H-NMR and C-NMR were used to elucidate the structures of the synthesized compounds. Most of the synthesized products were evaluated for their in vitro anticancer screening against HCT-116, HT-29 and HepG2 using the MTT colorimetric assay. The results indicated that compounds  and showed growth inhibition activity against HCT-116 with IC values of 3.80 ± 0.80, 3.65 ± 0.90 and 3.16 ± 0.90 μM, respectively, compared to harmine (IC = 2.40 ± 0.12 μM) and cisplatin (IC = 5.18 ± 0.94 μM) reference drugs. Also, compounds and showed promising IC values of 3.47 ± 0.79, 4.13 ± 0.51 and 7.24 ± 0.62 μM, respectively, against the more resistant human colorectal cancer (HT-29) cell line compared with harmine (IC = 4.59 ± 0.67 μM) and cisplatin (IC = 11.68 ± 1.54 μM). On the other hand, compounds and were the most active (IC values of 2.31± 0.43, 2.94 ± 0.62, 4.57 ± 0.85 and 9.86 ± 0.78 μM, respectively) against the hepatocellular carcinoma (HepG2) cell line compared with harmine (IC = 2.54 ± 0.82 μM) and cisplatin (IC = 41 ± 0.63 μM). The study also suggested that the mechanism of the anticancer action exerted by the most active compounds ( and ) inside HCT-116 cells was apoptosis through the Bcl-2 family. Thiazole scaffolds and showed anticancer activities in the micromolar range and are appropriate as a candidate for cancer treatment.

Background RNA-Seq is currently the most widely used tool to analyze whole-transcriptome profiles. There are numerous commercial kits available to facilitate preparing RNA-Seq libraries; however, it is still not clear how some of these kits perform in terms of: 1) ribosomal RNA removal; 2) read coverage or recovery of exonic vs. intronic sequences; 3) identification of differentially expressed genes (DEGs); and 4) detection of long non-coding RNA (lncRNA). In RNA-Seq analysis, understanding the strengths and limitations of commonly used RNA-Seq library preparation protocols is important, as this technology remains costly and time-consuming. Results In this study, we present a comprehensive evaluation of four RNA-Seq kits. We used three standard input protocols: Illumina TruSeq Stranded Total RNA and mRNA kits, a modified NuGEN Ovation v2 kit, and the TaKaRa SMARTer Ultra Low RNA Kit v3. Our evaluation of these kits included quality control measures such as overall reproducibility, 5′ and 3′ end-bias, and the identification of DEGs, lncRNAs, and alternatively spliced transcripts. Overall, we found that the two Illumina kits were most similar in terms of recovering DEGs, and the Illumina, modified NuGEN, and TaKaRa kits allowed identification of a similar set of DEGs. However, we also discovered that the Illumina, NuGEN and TaKaRa kits each enriched for different sets of genes. Conclusions At the manufacturers’ recommended input RNA levels, all the RNA-Seq library preparation protocols evaluated were suitable for distinguishing between experimental groups, and the TruSeq Stranded mRNA kit was universally applicable to studies focusing on protein-coding gene profiles. The TruSeq protocols tended to capture genes with higher expression and GC content, whereas the modified NuGEN protocol tended to capture longer genes. The SMARTer Ultra Low RNA Kit may be a good choice at the low RNA input level, although it was inferior to the TruSeq mRNA kit at standard input level in terms of rRNA removal, exonic mapping rates and recovered DEGs. Therefore, the choice of RNA-Seq library preparation kit can profoundly affect data outcomes. Consequently, it is a pivotal parameter to consider when designing an RNA-Seq experiment.