Efficacy of Saccharothrix algeriensis NRRL B-24137 to suppress Fusarium oxysporum f.sp. vasinfectum induced wilt disease in cotton.

Fusarium cotton wilt is a devastating disease of the cotton crop throughout the world, caused by Fusarium oxysporum f.sp. vasinfectum (FOV). Chemical control has many side effects, so, biological controls have been widely used for the management of Fusarium wilt. This study aimed to investigate the possible use of an actinomycetes Saccharothrix algeriensis (SA) NRRL B-24137 to control FOV. To access in-vitro anti-Fusarium ability of SA NRRL B-24137, dual culture assay, spore germination and seed germination tests were carried out. Following in-vitro investigations, several pot tests in a greenhouse environment were used to evaluate the biological control potential of SA NRRL B-24137 against FOV. Dual culture assay and spore germination revealed that SA NRRL B-24137 showed significant anti-Fusarium activity.During spore germination 87.77% inhibition of spore germination were observed. In pot experiments, SA NRRL B-24137 primed cotton seeds resulted in a 74.0% reduction in disease incidence. In soil there was a significant reduction in FOV spores in the presence of SA NRRL B-24137. Positive correlation was also observed on different concentrations of SA NRRL B-24137 towards FOV reduction. The results of this study showed that SA NRRL B-24137 has the potential to be employed as a biocontrol agent against Fusarium cotton wilt, improving cotton growth characteristics and yield.

Anti-cancer medicine shortages in an oncology tertiary hospital of Pakistan: A five-year retrospective study.

OBJECTIVE: Anti-cancer medicine shortages are advancing challenges for patients and hospitals. This study aims to evaluate anti-cancer and supportive medicine shortages in a tertiary hospital in Pakistan and propose solutions. METHOD: A retrospective observational research was performed in a tertiary care hospital in Pakistan from 2016 to 2020. Data was retrieved from the hospital database using a questionnaire regarding short medicines' generic name, brand, dosage, source, total source, frequency, causes, impact, management, and analyzed by Microsoft Excel 2013. RESULTS: Between January 2016 and December 2020, 43 individual medicine shortages were observed, with an average of 8.6 shortages per year. There were shortages of 22 medicines, including 8 anti-cancer (36.4%) and 14 supportive agents (63.6%). Total shortage days were 27,100, with an average of 1232 days (SD 757) per medicine. Supportive medicines' shortages were frequent, but oncology agents' shortages were constant. The most affected dosage form was injection. Cardiovascular drugs and alkylating agents were the most affected class in supportive and anti-cancer medicines, respectively. The use of "alternative medicine" and "patient needs based importation" were the most common mitigation strategies. CONCLUSION: Shortages of oncology medicines are challenging in Pakistan. The most prominent causes are the lack of updated governmental regulations, registration, and import issues. The tertiary care hospital has very few sources of supply, so it imports these drugs on a need basis to manage the shortages. But it is still concerning because of the huge financial burden on patients and institutions due to expensive import, and therapy become delayed as the import process takes time. Moreover, the most affected drug class was alkylating agents, and dosage was both injectable and oral medicines.

Advanced wearable biosensors for the detection of body fluids and exhaled breath by graphene.

Given the huge economic burden caused by chronic and acute diseases on human beings, it is an urgent requirement of a cost-effective diagnosis and monitoring process to treat and cure the disease in their preliminary stage to avoid severe complications. Wearable biosensors have been developed by using numerous materials for non-invasive, wireless, and consistent human health monitoring. Graphene, a 2D nanomaterial, has received considerable attention for the development of wearable biosensors due to its outstanding physical, chemical, and structural properties. Moreover, the extremely flexible, foldable, and biocompatible nature of graphene provide a wide scope for developing wearable biosensor devices. Therefore, graphene and its derivatives could be trending materials to fabricate wearable biosensor devices for remote human health management in the near future. Various biofluids and exhaled breath contain many relevant biomarkers which can be exploited by wearable biosensors non-invasively to identify diseases. In this article, we have discussed various methodologies and strategies for synthesizing and pattering graphene. Furthermore, general sensing mechanism of biosensors, and graphene-based biosensing devices for tear, sweat, interstitial fluid (ISF), saliva, and exhaled breath have also been explored and discussed thoroughly. Finally, current challenges and future prospective of graphene-based wearable biosensors have been evaluated with conclusion. Graphene is a promising 2D material for the development of wearable sensors. Various biofluids (sweat, tears, saliva and ISF) and exhaled breath contains many relevant biomarkers which facilitate in identify diseases. Biosensor is made up of biological recognition element such as enzyme, antibody, nucleic acid, hormone, organelle, or complete cell and physical (transducer, amplifier), provide fast response without causing organ harm.

Methionine-Controlled Impediment of Secondary Nucleation Leading to Nonclassical Growth within Self-Assembled De Novo Gold Nanoparticles.

The conventional key steps for seed-mediated growth of noble metal nanostructures involve classical and nonclassical nucleation. Furthermore, the surface of the seed catalytically enhances the secondary nucleation involving Au+ to Au0 reduction, thus providing in-plane growth of the seed. In contrast to this well-established growth mechanism, herein, we report the unique case of a methionine (Met)-controlled seed-mediated growth reaction, which rather proceeds via impeding secondary nucleation in the presence of citrate-stabilized gold nanoparticles (AuNPs). The interaction between the freshly generated Au+ and the thioether group of Met in the medium restricts the secondary nucleation process of further seed-catalyzed Au+ reduction to Au0. This incomplete conversion of Au+, as confirmed by X-ray photoelectron spectroscopy, results in a significant enhancement of the zeta (ζ) potential even at low Met concentrations. Nucleation of in situ generated small-sized particles (nAuNPs) takes place on the parent seed surface followed by their segregation from the seed. The self-assembly process of these nAuNPs arises from the aurophilic interaction among the Au+. Furthermore, the time-dependent growth of smaller particles to larger-sized particles through assembly and merging within the same self-assembly validates the nonclassical growth. This strategy has been successfully extended toward the seed-mediated growth reaction of AuNPs in the presence of three bio-inspired decameric peptides having varying numbers of Met residues. The study confirms the nucleation strategy even in the presence of a single Met residue in the peptide and also the self-assembly of nucleated particles with increasing Met residues within the peptide.

Preparedness to Combat Determinants of Underweight-Based Child Malnutrition in Flood-Affected Areas of Pakistan.

AIMS: Floods badly impact the food and nutrition security in developing countries. The role of the government and the impact of floods on the underweight status of children in the affected areas is not clear. We aimed to find the determinants of underweight in flood-affected areas of Khyber Pakhtunkhwa, Pakistan. METHODS: We used a multistage sampling technique and selected 656 households during in the flood-affected areas of Pakistan. Data were collected in the three most affected districts. A validated questionnaire was used to find socioeconomic and demographic information, hygiene, and sanitation information. We used logistic regression to find the determinants of underweight, controlling for confounders. RESULTS: The prevalence of global malnutrition based on underweight was 25.2%. The prevalence of underweight was higher in young age mothers (40.6%), younger age children (71.4%), large family size (28.4%), joint family (27%), and no toilet facility (28.9%). District Nowshera was at high risk of underweight based undernutrition, followed by district Charsadda compared to children belonging to Dera Ismail Khan. The significant risk factor that causes underweight was child lower age (p < 0.01), young age of mothers (p < 0.01), children access to unimproved water sources (p < 0.01), and location (districts) due to environmental and constant flood consequences (p < 0.01). CONCLUSION: In conclusion, risk factors of underweight should be appropriately targeted in the flood-hit areas of Pakistan. Governments should preallocate budgetary resources and enhance the emergency preparedness levels to facilitate the communities with flooding incidents and their aftermath in the shape of child underweight-based malnutrition.

Anti-anxiety Properties of Selected Medicinal Plants.

Exploration of new drugs targeting anxiety treatment is a major concern worldwide. Medicinal plants are being used as a potential source of novel drugs for anxiety disorders. The objective of this review is to provide information about the healing outcomes of anxiety treatment with natural products. Valeriana officinalis, Citrus aurantium, Commelina benghalensis, Achyranthes aspera, Mimosa pudica, Achillea millefolium, Nymphaea alba, Leonurus cardiac, Camellia sinensis, Turnera aphrodisiaca, Crataegus oxyacantha and Piper methysticum showed promising effects on anxiety in animal models. In clinical studies, passion flower, kava, valerian, St John's wort, and hwagandha showed the most positive results. More studies are needed for the exploration of the antianxiety of medicinal plants. In drugs derived from natural sources have explored many components that are playing an essential role in curing anxiety disorders and associated complications.

Development of Nonlaboratory-Based Risk Prediction Models for Cardiovascular Diseases Using Conventional and Machine Learning Approaches.

Criticism of the implementation of existing risk prediction models (RPMs) for cardiovascular diseases (CVDs) in new populations motivates researchers to develop regional models. The predominant usage of laboratory features in these RPMs is also causing reproducibility issues in low-middle-income countries (LMICs). Further, conventional logistic regression analysis (LRA) does not consider non-linear associations and interaction terms in developing these RPMs, which might oversimplify the phenomenon. This study aims to develop alternative machine learning (ML)-based RPMs that may perform better at predicting CVD status using nonlaboratory features in comparison to conventional RPMs. The data was based on a case-control study conducted at the Punjab Institute of Cardiology, Pakistan. Data from 460 subjects, aged between 30 and 76 years, with (1:1) gender-based matching, was collected. We tested various ML models to identify the best model/models considering LRA as a baseline RPM. An artificial neural network and a linear support vector machine outperformed the conventional RPM in the majority of performance matrices. The predictive accuracies of the best performed ML-based RPMs were between 80.86 and 81.09% and were found to be higher than 79.56% for the baseline RPM. The discriminating capabilities of the ML-based RPMs were also comparable to baseline RPMs. Further, ML-based RPMs identified substantially different orders of features as compared to baseline RPM. This study concludes that nonlaboratory feature-based RPMs can be a good choice for early risk assessment of CVDs in LMICs. ML-based RPMs can identify better order of features as compared to the conventional approach, which subsequently provided models with improved prognostic capabilities.

Anti-Hyperuricemic and Uricosuric Potential of Berberis vulgaris in Oxonate-Induced Hyperuricemic Rats.

Hyperuricemia is a metabolic disorder with characteristic elevated serum uric acid. Recently, several plant-based medicines are being used for the treatment of hyperuricemia. The study aimed to find the hypouricemic potential of Berberis vulgaris in in-vitro and in-vivo study models. In i n-vitro studies, xanthine oxidase inhibition assay was performed to evaluate IC50 value and capsule absorbance of the drug, respectively. For in-vivo experiment, the study comprised 15 groups of rats. In-vitro results revealed that significant xanthine oxidase inhibition was shown by Berberis vulgaris with an IC50 value of 272.73±.3 µg/mL. Similarly, oral administration of Berberis vulgaris with dosages of 250 and 500 mg/kg decreased serum and liver uric acid levels significantly in a dose- and time-dependent manner in oxonate-induced hyperuricemic rats. Furthermore, 3-day and 7-day administration of Berberis vulgaris showed more potential compared to 1-day administrations. The present study indicated marked hypouricemic effects of Berberis vulgaris in rats. Due to caveat of the small sample size, a firm assumption of the hypouricemic effect of Berberis vulgaris cannot be made. However, extensive study is needed to find out the exact molecular mechanism involved and to translate its effects into clinical trials for the further validation of the results.

Green Synthesis of Luminescent Gold-Zinc Oxide Nanocomposites: Cell Imaging and Visible Light-Induced Dye Degradation.

Green synthesis of gold-zinc oxide (Au-ZnO) nanocomposite was successfully attempted under organic solvent-free conditions at room temperature. Prolonged stirring of the reaction mixture introduced crystallinity in the ZnO phase of Au-ZnO nanocomposites. Luminescence properties were observed in these crystalline Au-ZnO nanocomposites due to in situ embedding of gold nanoparticles (AuNP) of 5-6 nm diameter on the surface. This efficient strategy involved the reduction of Au(III) by Zn(0) powder in aqueous medium, where sodium citrate (NaCt) was the stabilizing agent. Reaction time and variation of reagent concentrations were investigated to control the Au:Zn ratio within the nanocomposites. The reaction with the least amount of NaCt for a long duration resulted in Au-ZnO/Zn(OH)2 nanocomposite. X-ray photoelectron spectroscopy (XPS) confirmed the formation of Zn(OH)2 and ZnO in the same nanocomposite. These nanocomposites were reconnoitered as bioimaging materials in human cells and applied for visible light-induced photodegradation of rhodamine-B dye.

Nonclinical Features in Predictive Modeling of Cardiovascular Diseases: A Machine Learning Approach.

BACKGROUND: In the broader healthcare domain, the prediction bears more value than an explanation considering the cost of delays in its services. There are various risk prediction models for cardiovascular diseases (CVDs) in the literature for early risk assessment. However, the substantial increase in CVDs-related mortality is challenging global health systems, especially in developing countries. This situation allows researchers to improve CVDs prediction models using new features and risk computing methods. This study aims to assess nonclinical features that can be easily available in any healthcare systems, in predicting CVDs using advanced and flexible machine learning (ML) algorithms. METHODS: A gender-matched case-control study was conducted in the largest public sector cardiac hospital of Pakistan, and the data of 460 subjects were collected. The dataset comprised of eight nonclinical features. Four supervised ML algorithms were used to train and test the models to predict the CVDs status by considering traditional logistic regression (LR) as the baseline model. The models were validated through the train-test split (70:30) and tenfold cross-validation approaches. RESULTS: Random forest (RF), a nonlinear ML algorithm, performed better than other ML algorithms and LR. The area under the curve (AUC) of RF was 0.851 and 0.853 in the train-test split and tenfold cross-validation approach, respectively. The nonclinical features yielded an admissible accuracy (minimum 71%) through the LR and ML models, exhibiting its predictive capability in risk estimation. CONCLUSION: The satisfactory performance of nonclinical features reveals that these features and flexible computational methodologies can reinforce the existing risk prediction models for better healthcare services.

The molecular mechanism of a novel derivative of BTO-956 induced apoptosis in human myelomonocytic lymphoma cells.

Acute myeloid leukemia (AML) is a malignant cancer of the hematopoietic system. Although the effectiveness of arsenic compounds has been recognized and applied clinically, some patients are still found resistant to this chemotherapy. In this study, we investigated that a synthetic thyroid hormone analog (TA), 2-iodo-4-nitro-1-(o-tolyloxy) benzene, had a strong apoptosis effect on U937 cells. U937 cells were treated with TA, and examinted the generation of reactive oxygen species (ROS), dysfunction of mitochondria, expression of pro-apoptosis and anti-apoptosis, and cleavage of caspase-3 and Poly (ADP-ribose) polymerase (PARP). Further, it is also evaluated that insight molecular mechanism and signaling pathways involved in the study. It is found that TA significantly induced apoptosis in U937 cells through production of ROS, dysfunction of mitochondria, and activation of caspase cascade. It was also observed that MAPK signaling pathway including ERK, JNK, and P38 signals are involved in the induction of apoptosis. Moreover, marked activation of autophagy and ER stress markers such as LC3, P62, Beclin1 and GRP78, CHOP were observed, respectively. Pretreatment with ER stress inhibitor tauroursodeoxycholic acid (TUDCA) and autophagy inhibitor 3-Methyladenine (3-MA) have successfully attenuated and aggravated TA-induced apoptosis, respectively. We further confirmed the active involvement of ER stress and autophagy signals. In conclusion, TA induced apoptosis through ER stress and activation of autophagy, and the latter is not conducive to TA-induced cell death. Our results may provide a new insight into the strategic development of novel therapy for the treatment of AML.

Saccharothrix Algeriensis NRRL B-24137 Potentiates Chemical Fungicide Carbendazim in Treating Fusarium Oxysporum f.sp. Vasinfectum-Induced Cotton Wilt Disease.

Cotton (Gossypium hirsutum) wilt is one of the destructive disease caused by Fusarium oxysporum f. sp. vasinfectum and lead to 100% yield loss under favorable conditions. This study aims to estimate the potential of biological control agents Saccharothrix algeriensis NRRL B-24137 (SA) and chemical fungicides against cotton wilt pathogen under in-vitro and in-vivo conditions. The in-vitro study revealed that carbendazim showed maximum mycelia growth inhibition with a mean of 91% over control, which was further validated in glasshouse assay. In-vitro dual culture test of biocontrol agents with F. oxysporum determined that SA had a potential to inhibit mycelia growth by 68% compared to control. Further in glasshouse assay, the combination of the SA and carbendazim (10 µg/mL) showed a significant (p < 0.05) disease control. Moreover, results demonstrated that carbendazim and SA remarkably decreased the disease development up to 83% and subsequently, significant improvement was observed in the plant growth parameters (plant length, root length, and plant weight) compared to untreated plants. Conclusively, exploration and utilization of bioagent for fungal diseases in cotton may provide a better line with maximum efficacy and with lesser adverse effects, which will pave a way toward better consequences in fungal treatments.

Antibacterial and Toxicity Evaluation of Eastern Medicine Formulation Eczegone for the Management of Eczema.

The present study was conducted to evaluate the antibacterial activity, in vitro and in vivo cytotoxicity, cell viability and safety of Eastern Medicine coded medicinal formulation Eczegone comprising extracts of Azadirachta indica (Azin), Fumaria indica (Fuin), Sphaeranthus indicus (Spin) and Lawsonia inermis (Lain). This work also evaluated antibacterial activity of Eczegone formulation having above mentioned plants ethanolic extracts against different bacteria's by disk diffusion method. In vitro toxicity of Eczegone formulation was investigated by using human skin keratinocytes HaCaT cell line, crystal violet stained cells, and methyl tetrazolium cytotoxicity (MTT) assay. In vivo acute oral and dermal cytotoxicity was determined by using Swiss albino mice and albino rabbits, respectively. The Eczegone formulation showed antibacterial activity against 3 gram negative bacteria including Escherichia coli, Klebsiella pneumonia, Proteus vulgaris and a gram positive Staphylococcus aureus. We didn't observe any toxic effect of Eczegone formulation on the skin keratinocytes. Furthermore, the Ezcegone formulation was non-irritant according to draize score (OECD TG404, 2002). After rigorous safety evaluation by in vitro and in vivo acute oral and dermal toxicity analysis, we concluded that Eczegone formualtion possessses antibacterial effects and is safe, non-toxic, non-irritant, and the drug would be subjected for further biochemical and clinical studies.

Melatonin triggers the anticancer potential of phenylarsine oxide via induction of apoptosis through ROS generation and JNK activation.

Melatonin, a safe endogenous hormone and a natural supplement, has recently been recognized to have antiproliferative effects and the ability to sensitize cells to other anticancer therapies. Phenylarsine oxide (PAO) has anticancer potential but it is considered as a toxic agent. In this study we combined melatonin to reduce the toxicity while securing the anti-cancer effects of PAO. Cell viability was determined by MTT assay, whereas cytotoxic assays were performed using an LDH cytotoxicity assay kit. Cell cycle analysis, Annexin V/PI staining, the mitochondrial membrane potential (MMP), mitochondrial calcium and reactive oxygen species (ROS) generation were analyzed using flow cytometry. Sytox stained cells were visualized by fluorescence microscopy and the expression of proteins was detected by western blotting. Melatonin increased the anticancer potential of PAO by decreasing the cell viability and increasing LDH release in various cancer cells. The mode of cell death was determined to be typical apoptosis, as evidenced by Annexin V/PI-stained cells, PARP cleavage, and caspase-3 activation, and with significant modulations in the expression of proapoptotic, antiapoptotic and cell cycle-related proteins. ROS generation played a critical role in induction of cell death by this combined treatment, which is validated by reversal of cytotoxicity upon cotreatment with NAC. Furthermore, the activation of MAPKs, especially JNK, contributed to the induction of cell death, accompanied by endoplasmic reticulum stress and autophagy, affirmed by the abrogation of cytotoxicity after JNK-IN-8 and TUDCA application. Melatonin showed promising potential as a chemotherapeutic agent in combination with PAO to achieve a better anticancer response.

Tricuspid annular plane systolic excursion is correlated with poor outcome in surgery for rheumatic heart valvular disease.

BACKGROUND: Right ventricular (RV) function is a major determinant of clinical outcome, but its function indices have not been studied well in surgery for rheumatic valvular heart disease. The aim of this study was to determine the correlation of tricuspid annular plane systolic excursion (TAPSE) with outcome of rheumatic heart valve surgery. METHODS: A prospective comparative study was conducted including 100 eligible patients who were divided into two groups based on RV function as assessed by TAPSE measured by two-dimensional (2D) echocardiography preoperatively. Those with TAPSE less than 15 mm were included in group 1 and those with TAPSE of 15 or more were included in group 2. RESULTS: 50 patients were included in group 1 and 50 patients in group 2. Mean age of the patients was 56.78 ± 15.21 years in group 1 and 54.46 ± 15.03 years in group 2 (P = 0.444). 34 (34%) patients underwent aortic valve replacement (AVR), 35 (35%) underwent both aortic and mitral valves replacement, and 31 (31%) ones had mitral valve replacement (MVR). A significant difference was found between the duration of ventilation (5.15 ± 2.80 hours in group 1 vs. 3.72 ± 2.71 hours in group 2, P = 0.001), postoperative inotropic requirement [more than 24 hours in 18 (36%) patients in group 1 vs. 7 (14%) patients in group 2, P = 0.003], total intensive care unit (ICU) stay (8.92 ± 3.62 days in group 1 vs. 5.20 ± 2.06 days in group 2, P = 0.001), and mortality [7 (14%) in group 1 vs. 2 (4%) in group 2, P = 0.038]. CONCLUSION: TAPSE less than 15 mm in patients undergoing surgical correction for rheumatic valvular heart disease leads to poor outcomes. These patients need special attention perioperatively.

Tryptophan-Stabilized Au-FexOy Nanocomposites as Electrocatalysts for Oxygen Evolution Reaction.

Au-FexOy nanocomposites with a variable gold-to-iron ratio were stabilized with l-tryptophan. The synthetic methodology is based on the facile redox reaction between Au(III) and Fe(0) in the presence of gold nanoparticle as a seed at room temperature in an aqueous medium. The synthesis results in the deposition of Au nanoparticles on the surface of iron oxide layers. Composition variation in the nanocomposites was obtained by controlling the seed amount and reducing agent. These nanocomposites are used as electrocatalysts for the thermodynamically unfavorable oxygen evolution reaction (OER) from water. Among the nanocomposites, the most efficient OER activity was observed from the nanocomposite 12. The content of iron with respect to gold is at the maximum in the nanocomposite, which was obtained from the reaction with a minimum seed concentration and maximum reducing agent.

Comparative Clinical Characteristics of Rheumatic Heart Disease Patients Undergoing Surgical Valve Replacement.

Background To assess the prevalence patterns of isolated/mixed rheumatic valvular lesions and associated risk factors among rheumatic heart disease (RHD) patients undergoing surgical valve replacement. Methods An analytical cross-sectional design was used. Purposive sampling was used to select 87 RHD patients who underwent a first-time valve replacement for mitral, aortic, or both valves between April 1 and October 20, 2016, at Punjab Institute of Cardiology, Lahore, Pakistan. Patients with systemic hypertension, diabetes mellitus type-II, congenital heart defects, coronary artery disease, non-rheumatic valvular degeneration, positive test for hepatitis C, or undergoing concomitant coronary artery bypass graft or a 'redo' valve replacement procedure were excluded. A proforma was used to collect preoperative data on patients' demographics, laboratory investigations, electrocardiogram (ECG), and transthoracic echocardiography reports. Results Age (mean ± S.D.) was 32.79 ± 13.06 years, which was divided into four quartile-based groups. Forty-six (52.9%) cases were males. The majority (56.3%) of patients underwent mitral valve replacement. Mitral regurgitation (MR, 80%) was the most common lesion. Of 71 available ECGs, atrial fibrillation was observed in 46.5% cases. Increasing age group was negatively correlated with MR severity (τc = -0.188, p-value = 0.033) and positively with aortic stenosis (AS) severity (τc = 0.141, p-value = 0.010). No significant elevations were observed for anti-streptolysin O titer, C-reactive protein, and leukocyte count, though the erythrocyte sedimentation rate was abnormally high in 46.94% cases. Conclusions MR was the most common lesion. MR was more severe in younger patients whilst AS was more severe in older cases. There is little evidence of ongoing residual inflammation.

Gold Nanoflower for Selective Detection of Single Arginine Effect in α-Helix Conformational Change over Lysine in 310-Helix Peptide.

Hydroxylamine-based growth reaction in the presence of natural l-amino acids (9 mM) and gold nanoparticle seed mostly produce aggregated or nonaggregated gold nanostructures except the cases of immediate precipitation with aspartic acid, glutamic acid, cysteine, and tyrosine. Among the other amino acids, arginine shows the control growth reaction to form gold nanoflower from gold nanoparticle seeds, which were preincubated with amine-modified DNA (NH2-oln). The absorbance trend with NH2-oln in the presence of arginine is similar to the aggregation behavior in the presence of histidine and methionine. The formations of gold nanoflower with arginine and aggregation due to histidine and methionine in the presence of NH2-oln were sorted out with lower concentration (50 µM) of these amino acids. This observation was successfully transferred to differentiate 310-helical Ac-(AAAAK)3A-NH2 from α-helical Ac-(AAAAR)3A-NH2. The concept was further applied for the detection of single arginine modification closest to the carboxy terminus of 310-helical Ac-(AAAAK)3A-NH2 peptide for maximum conformational change toward α-helix.

Aluminum chloride causes 5-fluorouracil resistance in hepatocellular carcinoma HepG2 cells.

Chemoresistance is one of the major obstacles in chemotherapy-based hepatocellular carcinoma (HCC) intervention. Aluminum (Al) is an environmental pollutant that plays a vital role in carcinogenesis, tumorigenesis, and metastasis. However, the effect of Al on chemoresistance remains unknown. 5-Fluorouracil (5-FU) is a widely used antitumor drug. Therefore, we investigated the effects of aluminum chloride (AlCl3 ) on the chemoresistance of HepG2 cells to 5-FU and explored the underlying mechanisms of these effects. The results demonstrated that AlCl3 pretreatment attenuated 5-FU-induced apoptosis through Erk activation and reversed 5-FU-induced cell cycle arrest by downregulating p-Chk2Thr68 levels. In addition, AlCl3 markedly increased the levels of proteins associated with cell migration, such as MMP-2 and MMP-9. Further investigation demonstrated that an Erk inhibitor (U0126) reversed the AlCl3 -induced decrease in apoptosis, enhancement of cell cycle progression, promotion of cell migration, and attenuation of oxidative stress. In summary, AlCl3 induced chemoresistance to 5-FU in HepG2 cells. The present study suggests a potential influence of AlCl3 on 5-FU therapy. These findings may help others to understand and properly address the resistance of HCC to chemotherapeutic agents.

Protective effect of dihydromyricetin on hyperthermia-induced apoptosis in human myelomonocytic lymphoma cells.

Dihydromyricetin (DMY) is a traditional herbal medicine, with a wide range of biological activities. Extreme hyperthermia (HT) can suppress the immune system; thus, protection of the immune system is beneficial in heat-related diseases, including heatstroke. In our study, we revealed the protective effect of DMY against HT-induced apoptosis and analysed the underlying molecular mechanisms. We incubated human myelomonocytic lymphoma U937 cells at 44 °C for 30 min with or without DMY and followed by further incubation for 6 h at 37 °C. Cell viability was determined by the CCK-8 assay. DMY did not cause any cytotoxic effects in U937 cells even at high doses. HT treatment alone induced significant apoptosis, which was detected by DNA fragmentation and Annexin V/PI double staining. Mitochondrial dysfunction was identified by loss of mitochondrial membrane potential (MMP) during heat stimulation. Apoptotic related proteins were involved, truncated Bid and caspase-3 were upregulated, and Mcl-1 and XIAP were downregulated. We also identified the related signalling pathways, such as the MAPK and PI3K/AKT pathways. However, changes in HT were dramatically reversed when the cells were pretreated with DMY before exposure to HT. Overall, MAPKs and PI3K/AKT signalling, mitochondrial dysfunction, and caspase-mediated pathways were involved in the protective effect of DMY against HT-induced apoptosis in U937 cells, which was totally reversed by DMY pretreatment. These findings indicate a new clinical therapeutic strategy for the protection of immune cells during heatstroke.