Pomiferin targeting SLC9A9 based on histone acetylation modification pattern is a potential therapeutical option for gastric cancer with high malignancy.

Changes in histone acetylation status are associated with gastric cancer (GC) progression. Pomiferin is a natural flavonoid, however, the specific role of pomiferin in the treatment of GC is still unclear, and its targets are not well clarified. In this work, the prognostic genes related with histone acetylation in GC were screened by univariate Cox analysis. Next, a risk model of was constructed using least absolute shrinkage and selection operator-Cox regression analyses, and multivariate Cox analysis was used for identifying the independent risk factor. Molecular docking was performed using AutoDock Vina to validate the interaction between solute carrier family 9 member A9 (SLC9A9) and pomiferin. In vitro and in vivo models were applied to investigate the tumor-suppressive role of pomiferin against GC. The inhibitory effects of pomiferin on EGFR/PI3K/AKT signaling were valdiated by Western blotting, immunofluorescence staining and qPCR. Here, a prognostic risk model based on histone acetylation regulators was established, and SLC9A9 was identified as a risk factor associated with histone acetylation status in GC. SLC9A9 expression was associated with abnormal immune microenvironment of tumor. Pomiferin had a high binding affinity with SLC9A9, and both pomiferin treatment and depletion of SLC9A9 repressed the malignant phenotypes of GC cells. Mechanistically, pomiferin inactivates EGFR/PI3K/AKT signaling in GC cells. In summary, SLC9A9, as a indicator of abnormal histone acetylation status of GC, functions as an oncogenic factor. Pomiferin binds with SLC9A9 to inactivate EGFR/PI3K/AKT pathway, to block GC progression, suggesting it is a promising drug for the patients with highly malignant GC.

Health information-seeking behavior in patients with coronary artery disease: Activating methods.

INTRODUCTION: Coronary artery disease (CAD) has a high mortality rate worldwide, and continuous health behavior practice and careful management are required owing to risks such as rapid changes in symptoms and emergency hospitalization. The utilization of health-related information is an important factor for long-term disease management in patients with CAD. For this purpose, an understanding of health information-seeking behavior is needed first. METHODS: This study analyzed data from the 2021 Korea Medical Panel Survey, and logistic regression analysis was conducted to confirm the factors influencing the health information-seeking behavior of patients with CAD. RESULTS: The health information-seeking behavior of patients with CAD differed according to demographic characteristics, and differences in preferred information use were confirmed. Finally, it was identified that insufficient levels of health literacy were a major reason for CAD patients not engaging in health information-seeking behaviors (OR, 0.17; 95% CI, 0.09-0.33; p < 0.001). CONCLUSION: This study suggests that to improve health information-seeking behaviors, the application of education and intervention programs to increase the level of health literacy is necessary.

Penthorum chinense Pursh inhibits ferroptosis in cellular and Caenorhabditis elegans models of Alzheimer's disease.

BACKGROUND: Ferroptosis, a unique type of cell death triggered by iron-dependent lipid peroxidation, plays a critical role in the pathogenesis of Alzheimer's disease (AD), a debilitating condition marked by memory loss and cognitive impairment due to the accumulation of beta-amyloid (Aß) and hyperphosphorylated Tau protein. Increasing evidence suggests that inhibitors of ferroptosis could be groundbreaking in the treatment of AD. METHOD: In this study, we established in vitro ferroptosis using erastin-, RSL-3-, hemin-, and iFSP1-induced PC-12 cells. Using MTT along with Hoechst/PI staining, we assessed cell viability and death. To determine various aspects of ferroptosis, we employed fluorescence probes, including DCFDA, JC-1, C11 BODIPY, Mito-Tracker, and PGSK, to measure ROS production, mitochondrial membrane potential, lipid peroxidation, mitochondrial morphology, and intracellular iron levels. Additionally, Western blotting, biolayer interferometry technology, and shRNA were utilized to investigate the underlying molecular mechanisms. Furthermore, p-CAX APP Swe/Ind- and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, along with Caenorhabditis elegans (C. elegans) strains CL4176, CL2331, and BR5270, were employed to examine ferroptosis in AD models. RESULTS: Here, we conducted a screening of our natural medicine libraries and identified the ethanol extract of Penthorum chinense Pursh (PEE), particularly its ethyl acetate fraction (PEF), displayed inhibitory effects on ferroptosis in cells. Specifically, PEF inhibited the generation of ROS, lipid peroxidation, and intracellular iron levels. Furthermore, PEF demonstrated protective effects against H2O2-induced cell death, ROS production, and mitochondrial damage. Mechanistic investigations unveiled PEF's modulation of intracellular iron accumulation, GPX4 expression and activity, and FSP1 expression. In p-CAX APP Swe/Ind and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, PEF significantly reduced cell death, as well as ROS and lipid peroxidase production. Moreover, PEF ameliorated paralysis and slowing rate in Aß and Tau transgenic C. elegans models, while inhibiting ferroptosis, as evidenced by decreased DHE intensity, lipid peroxidation levels, iron accumulation, and expression of SOD-3 and gst-4. CONCLUSION: Our findings highlight the suppressive effects of PEF on ferroptosis in AD cellular and C. elegans models. This study helps us better understand how ferroptosis affects AD and emphasizes the potential of PCP as a candidate for AD intervention.

Etanercept treatment for pediatric toxic epidermal necrolysis induced by deflazacort: a case report and literature review.

Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disorder commonly caused by drugs. TEN is often treated with corticosteroids, intravenous immunoglobulin (IVIG), or cyclosporine; however, the efficacy of these treatments is controversial. Etanercept (a TNF-α antagonist) was proven to decrease skin-healing time in a randomized clinical trial. Herein, we report the case of a 44-month-old boy who developed TEN due to deflazacort as the probable culprit drug and was successfully treated with etanercept. The patient presented to the emergency department complaining of erythematous maculopapular rashes and vesicles all over the face and body, with vesicles on the hands, feet, and trunk. Symptoms started 4 days before presentation, with edema of the upper lip, which progressed to erythematous macules over the body. He was started on deflazacort for nephrotic syndrome 21 days before the visit. Approximately 20% of the body surface area (BSA) was covered by vesicular lesions. Under the diagnosis of Steven Johnson syndrome/TEN, deflazacort was discontinued, and intravenous dexamethasone (1.5 mg/kg/day), a 5-day course of IVIG (0.4 mg/kg/day), and cyclosporine (3 mg/kg/day) were administered. The lesions seemed to be stationary for 3 days, but on the 6th day of hospitalization, when IVIG was discontinued, the vesicular lesions progressed to approximately 60% of the BSA. Etanercept 0.8 mg/kg was administered subcutaneously. Lesions stopped progressing, and bullous lesions started epithelialization. However, on the 15th day, around 30% of the BSA was still involved; thus, a second dose of etanercept was administered. No acute or sub-acute complications were observed. In conclusion, the use of etanercept in children with TEN that is not controlled with conventional therapy is both effective and safe.

A cochleate formulation optimized by D-optimal mixture design enhances oral bioavailability of Revaprazan.

A cochleate formulation was developed to enhance the oral bioavailability of revaprazan (RVP). Dimyristoyl phosphatidylcholine (DMPC) liposome containing dicetyl phosphate (DCP) successfully formed a cochleate after treatment with CaCl2, whereas that containing sodium deoxycholate did not. Cochleate was optimised using a D-optimal mixture design with three independent variables-DMPC (X1, 70.58 mol%), cholesterol (X2, 22.54 mol%), and DCP (X3, 6.88 mol%)-and three response variables: encapsulation efficiency (Y1, 76.92%), released amount of free fatty acid at 2 h (Y2, 39.82%), and released amount of RVP at 6 h (Y3, 73.72%). The desirability function was 0.616, showing an excellent agreement between the predicted and experimental values. The cylindrical morphology of the optimised cochleate was visualised, and laurdan spectroscopy confirmed the dehydrated membrane interface, showing an increased generalised polarisation value (approximately 0.5) over small unilamellar vesicle of RVP (RVP-SUV; approximately 0.1). The optimised cochleate showed greater resistance to pancreatic enzyme than RVP-SUV. RVP was released in a controlled manner, achieving approximately 94% release in 12 h. Following oral administration in rats, the optimised cochleate improved the relative bioavailability of RVP by approximately 274%, 255%, and 172% compared to RVP suspension, a physical mixture of RVP and the cochleate, and RVP-SUV, respectively. Thus, the optimised cochleate formulation might be a good candidate for the practical development of RVP.

Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease-modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD. METHODS: The neuroprotective effect of CFE in H2O2- or 6-OHDA-induced PC-12 cells and α-synuclein-overexpressing PC-12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α-synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α-synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging-related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria. RESULTS: In cellular models of PD, CFE significantly attenuated H2O2- or 6-OHDA-induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α-synuclein in wide type (WT)-, A53T-, A30P-, or E46K-α-synuclein-overexpressing PC-12 cells. Our further findings reveal that CFE administration reduced α-synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6-OHDA-induced degeneration in BZ555 worms, extended lifespan, delayed aging-related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo. CONCLUSION: Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD.

A case-crossover study on the impact of air pollution on the number of pediatric respiratory outpatient and emergency visits in a hospital in Shanghai / 公共卫生与预防医学

Objective To investigate the correlation between the concentration of air pollutants (PM10, SO2, NO2) and the number of outpatient and emergency visits for pediatric respiratory diseases in a general hospital in Shanghai. Methods Data including pediatric respiratory disease outpatient and emergency visits in a hospital in Pudong New Area of Shanghai from May 1, 2013 to March 20, 2022 were collected. Daily concentration of air pollutants including PM10, SO2 and NO2 and meteorological data in Pudong New Area during the same period were collected. A case-crossover study with distributed lag non-linear model was conducted to explore the correlation between air pollutants (PM10, SO2, NO2) and the number of outpatient and emergency visits for pediatric respiratory diseases. Results The concentrations of PM10, SO2 and NO2 were positively with the number of outpatient and emergency visits for pediatric respiratory diseases. The strongest cumulative effect was observed on six days lag (Lag0-5) for PM10. For a 10 μg/m3 increase of the concentrations of PM10, the corresponding increase of cumulative pediatric respiratory disease outpatients was 1.10% (95%CI:0.97%, 1.23%) in Lag0-5. The strongest cumulative effect was observed on eight days lag (Lag0-7) for SO2 and NO2. For a 10 μg /m3 increase of the concentrations of SO2 and NO2, the corresponding increase of cumulative pediatric respiratory disease outpatients was 5.64% (95%CI:5.16%, 6.13%) and 5.41% (95%CI:5.15%, 5.66%) in Lag 0-7, respectively. The association of PM10 and SO2 with the number of pediatric respiratory disease visits in males was significantly stronger than that in females. The impact of PM10 on the number of pediatric respiratory disease visits in children aged 0-6 was higher than that in children aged 7-14, while the impact of SO2 and NO2 on the number of pediatric respiratory disease visits in children aged 7-14 was higher than that in children aged 0-6. Conclusion The concentration of ambient PM10, SO2, and NO2 is positively correlated with outpatient and emergency visits for pediatric respiratory diseases, with obvious lag and cumulative effect. Boys and children aged 0-6 are more susceptible to the hazard of air pollution.

Structural identification of the related substances in phloroglucinol injection by two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry / 药学学报

This study aimed to identify the related substances of phloroglucinol injection by two-dimensional liquid chromatography quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS). The first-dimensional separation was carried out on an HSS T3 (250 mm × 4.6 mm, 5 μm) column by gradient elution using 1.36 g·L-1 potassium dihydrogen phosphate buffer solution (pH adjusted to 3.0 with diluted phosphoric acid) and acetonitrile as the mobile phases. The separated components were then trapped in switch valve tube lines respectively and delivered to the second-dimensional desalting gradient elution which was performed with a BDS C18 (100 mm × 4.6 mm, 2.4 μm) column using 0.1% formic acid and methanol as the mobile phases. After rapid desalting, electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry was used for determining the accurate masses and elemental compositions of the parents and their product ions for both phloroglucinol and its related substance. Structures of the related substances were then figured out by mass spectrometry elucidation, organic reaction mechanism analysis, and/or comparison with reference substances. Under the established analytical conditions, phloroglucinol and its related substances were adequately separated, 17 main related substances were detected and identified in the injection and its stressed samples for the first time. The identification results can provide reference for the quality control of phloroglucinol injection.

Antiproliferative Activity of Krukovine by Regulating Transmembrane Protein 139 (TMEM139) in Oxaliplatin-Resistant Pancreatic Cancer Cells.

Krukovine (KV) is an alkaloid isolated from the bark of Abuta grandifolia (Mart.) Sandw. (Menispermaceae) with anticancer potential in some cancers with KRAS mutations. In this study, we explored the anticancer efficacy and mechanism of KV in oxaliplatin-resistant pancreatic cancer cells and patient-derived pancreatic cancer organoids (PDPCOs) with KRAS mutation. After treatment with KV, mRNA and protein levels were determined by RNA-seq and Western blotting, respectively. Cell proliferation, migration, and invasion were measured by MTT, scratch wound healing assay, and transwell analysis, respectively. Patient-derived pancreatic cancer organoids (PDPCOs) with KRAS mutations were treated with KV, oxaliplatin (OXA), and a combination of KV and OXA. KV suppresses tumor progression via the downregulation of the Erk-RPS6K-TMEM139 and PI3K-Akt-mTOR pathways in oxaliplatin-resistant AsPC-1 cells. Furthermore, KV showed an antiproliferative effect in PDPCOs, and the combination of OXA and KV inhibited PDPCO growth more effectively than either drug alone.

Pregnancy complicated with primary hyperparathyroidism: a report of 3 cases / 中华全科医师杂志

Clinical data of 3 pregnant women with primary hyperparathyroidism admitted in Jinan Maternal and Child Health Hospital from 2013 to 2021 were retrospectively reviewed. Hyperparathyroidism was diagnosed during pregnancy in all 3 cases. The clinical manifestations were non-specific, such as nausea, vomiting, anorexia, and fatigue. Patients also had gallbladder stones (1 case), gallbladder polyps (1 case), and renal parenchyma changes (2 cases). The hypercalcemia crisis occurred in all 3 cases, the blood Ca 2+ levels were 4.11 mmol/L, 2.92-3.82 mmol/L and 3.49-4.10 mmol/L, respectively; and preeclampsia developed in 2 cases. Sudden death occurred in case 1 who did not receive effective treatment during pregnancy; blood calcium was well controlled during pregnancy in case 2, and her neonate had hypocalcemia with good prognosis; case 3 underwent surgical treatment in early pregnancy, and then had missed abortion. Pathological examination revealed parathyroid tumors in all 3 cases.

Triaging patients in the outbreak of COVID-2019 / 中国感染控制杂志

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

Correlation between in-vivo mercury exposure from Cinnabaris and memory disorders in juvenile rat / 中国药科大学学报

@#Cinnabaris(α-HgS) is a mineral traditional Chinese material medica, as a tranquilizer and sedative, which is widely used in combination with herbs for the treatment of children high fever and convulsion.However, a large amount of mercury in Cinnabaris poses a potential risk to the immature central nervous system of children and probably causes severe memory disorders.Inthisstudy,three groups of juvenile rats were given low, medium, and high doses of Cinnabaris by oral gavage once a day for 14 continuous weeks, respectively.The blood mercury concentrations of the rats at different growth phases were monitored by atomic fluorescence spectrometry.The brain structural and functional changes related to the memory functions were investigated through HE staining and Morris water-maze test. Correlation analysis was conducted to clarify the dose- mercury exposure-toxic effect relationship of Cinnabaris and memory disorders.It was found thatthe blood mercury levels increased in both time- and dose-dependent manner.After the 14-week continuous administration of Cinnabaris, the pathological lesions in hippocampal neurons of rats in the high dose group were observed including pyknosis and disordered cell arrangement.In the Morris water-maze test, compared with the control group, rats in the high dose group exhibited the significantly prolonged latency to find the platform and the target quadrant, and the time spent in the target quadrant was obviously shortened. Thus, the significant correlations were established between Cinnabaris dose and mercury exposure,mercury exposure and memory disorders, respectively. In conclusion, the long-term and overdose administration of Cinnabaris in juvenile rats can increase the in-vivo mercury level, destroy the normal hippocampal morphological structure, and lead to memory disorders. This study provided scientific references for the potential mercury poisoning risks pharmacovigilance of Cinnabaris-containing paediatric formulations.

In vitro release of paclitaxel derivative liposome by paddle membrane binding assay / 中国药科大学学报

@#The in vitro release is an important index to evaluate the quality of liposome formulation.Currently, there is no evaluation method for the in vitro release of liposome in pharmacopoeia of various countries, which leads to the lack of unified standard and safety guarantee for the quality evaluation of liposome formulation.Taking the self-made paclitaxel derivative liposomes as an example, the paddle membrane binding method established by optimizing external release conditions was used to simulate the complete release of paclitaxel derivative drugs in 12 hours under physiological conditions.The results showed that using 0.5% SDS-HEPES as the release medium and a dialysis bag with a molecular weight cutoff of 1 000 kD to release the liposome solution met the requirements and had discrimination ability, providing a reference for the development of drug-loaded liposomes release methods in vitro.

A Systematic Review of the Effects of Aromatherapy on Depression and Anxiety in Postmenopausal Women

Purpose@#This systematic review aimed to investigate the effects of aromatherapy interventions on depression and anxiety in menopausal women. @*Methods@#This study adhered to PRISMA (preferred reporting items of systemic reviews and meta-analysis) guidelines. Relevant studies published between 1994 and 2002 were searched in PubMed, Embase, Cochrane Library, CINAHL, Google Scholar, DBPIA, KISS, and RISS databases. Search criteria included the mesh terms 'aromatherapy menopause women depression anxiety.' The review included randomized and nonrandomized studies of women who were menopausal or postmenopausal and received aromatherapy intervention for depression and anxiety associated with symptoms of menopause. The extracted literature was evaluated via quality appraisal checklists of ROB 2 (Risk of Bias 2.0) and ROBINS-1 (Risk Of Bias In Non-Randomized Studies - of Interventions) and visualized using a risk-of-bias visualization tool. @*Results@#The review included 6 randomized controlled studies and 2 quasi-experimental studies. The results showed that aromatherapy massage and inhalation therapy were effective in reducing depression and had beneficial effects in reducing anxiety, improving quality of sleep, and menopausal symptoms in menopausal women. @*Conclusion@#Interventions using aromatic essential oils to massage the hands, arms, back, and scalp or inhalation of aromatic oils from clothing, necklaces, and bedding might be beneficial for the emotional health of menopausal women. Women health professionals should consider applying aromatherapy to menopausal women to improve emotional health, sleep, and menopausal symptoms.

Cloning and functional analysis of IPI gene from Fritillaria unibracteata Hsiao et K. C. Hsia / 药学学报

An open reading frame (ORF) of isopentenyl-diphosphate delta isomerase gene (FuIPI) was cloned from Fritillaria unibracteata Hsiao et K. C. Hsia. (F. unibracteata). Furthermore, the bioinformatics and functional analyses of FuIPI were performed in this study. The result showed that, the ORF of FuIPI gene was 825 bp, encoding a polypeptide of 274 amino acids in length, with a relative molecular mass of about 31 kD and a theoretical isoelectric point of 5.61. Sequence analysis showed that FuIPI contained conserved structural domains and key residues involved in the catalyzing process. The phylogenetic analysis exhibited that FuIPI was closely related to IPIs of Dendrobium officinale and Musa acuminate. Real-time PCR analysis showed that FuIPI was distributed in different tissues of F. unibracteata, but had the highest transcriptional level in leaves, followed by stems, bulbs, and flowers. Furthermore, the FuIPI protein was successfully expressed in Escherichia coli BL21(DE3). The purified FuIPI protein successfully catalyzed the conversion from isopentenyl diphosphate (IPP) to dimethylallyl pyrophosphate (DMAPP). The above results provided a theoretical basis for further investigation of the molecular role of FuIPI in the biosynthesis of alkaloids.

A new dihydrochalcone from Humulus scandens / 中国中药杂志

To study the chemical constituents from the stems and leaves of Humulus scandens, this study isolated thirteen compounds by different chromatographic methods including silica gel column, ODS, Sephadex LH-20 and preparative HPLC. Based on comprehensive analysis, the chemical structures were elucidated and identified as citrunohin A(1), chrysosplenetin(2), casticin(3), neoechinulin A(4), ethyl 1H-indole-3-carboxylate(5), 3-hydroxyacetyl-indole(6),(1H-indol-3-yl) oxoacetamide(7), inonotusic acid(8), arteannuin B(9), xanthotoxol(10), α-tocopherol quinone(11), eicosanyl-trans-p-coumarate(12), and 9-oxo-(10E,12E)-octadecadienoic acid(13). Among them, compound 1 was a new dihydrochalcone, and the other compounds were obtained from H. scandens for the first time.

Production of polyhydroxyalkanoates containing monomers conferring amorphous and elastomeric properties from renewable resources: Current status and future perspectives.

Petrochemical-based plastics cause environmental pollution and threaten humans and ecosystems. Polyhydroxyalkanoate (PHA) is considered a promising alternative to nondegradable plastics since it is eco-friendly and biodegradable polymer having similar properties to conventional plastics. PHA's material properties are generally determined by composition and type of monomers in PHA. PHA can be designed in tailor-made manner for their suitable application areas. Among many monomers in PHAs, ω-hydroxalkanoates such as 3-hydroxypropionate (3HP), 4-hydroxybutyrate (4HB), 5-hydroxyvalerate (5HV), and 6-hydroxyhexanoate (6HHx) and medium-chain-length 3-hydroxyalkanoate such as 3-hydroxyhexanoate (3HHx) and 4-hydroxyvalerate (4HV), have been examined as potential monomers able to confer amorphous and elastomer properties when these are incorporated as comonomer in poly(3-hydroxybutyrate) copolymer that has 3HB as main monomer along with comonomers in different monomer fraction. Herein, recent advances in production of PHAs designed to have amorphous and elastomeric properties from renewable sources such as lignocellulose, levulinic acid, crude glycerol, and waste oil are discussed.

Enhanced oral absorption of insulin: hydrophobic ion pairing and a self-microemulsifying drug delivery system using a D-optimal mixture design.

The lipophilicity of a peptide drug can be considerably increased by hydrophobic ion pairing with amphiphilic counterions for successful incorporation into lipid-based formulations. Herein, to enhance the oral absorption of insulin (INS), a self-microemulsifying drug delivery system (SMEDDS) formulation was developed. Prior to optimization, INS was complexed with sodium n-octadecyl sulfate (SOS) to increase the loading into the SMEDDS. The INS-SOS complex was characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and its dissociation behavior. The SMEDDS was optimized using a D-optimal mixture design with three independent variables including Capmul MCM (X1, 9.31%), Labrasol (X2, 49.77%), and Tetraglycol (X3, 40.92%) and three response variables including droplet size (Y1, 115.2 nm), INS stability (Y2, 46.75%), and INS leakage (Y3, 17.67%). The desirability function was 0.766, indicating excellent agreement between the predicted and experimental values. The stability of INS-SOS against gastrointestinal enzymes was noticeably improved in the SMEDDS, and the majority of INS remained in oil droplets during release. Following oral administration in diabetic rats, the optimized SMEDDS resulted in pharmacological availabilities of 3.23% (50 IU/kg) and 2.13% (100 IU/kg). Thus, the optimized SMEDDS is a good candidate for the practical development of oral delivery of peptide drugs such as INS.

Citri Reticulatae Semen Extract Promotes Healthy Aging and Neuroprotection via Autophagy Induction in Caenorhabditis elegans.

Nutrition intervention has emerged as a potential strategy to delay aging and promote healthy longevity. Citri Reticulatae Semen (CRS) has diverse beneficial effects and has been used for thousands of years to treat pain. However, the health benefits of CRS in prolonging health span and improving aging-related diseases and the exact mechanisms remain poorly characterized. In this study, Caenorhabditis elegans (C. elegans) was used as a model organism to study the antiaging and health span promoting activities of 75% ethanol extract of CRS (CRSE). The results showed that treatment with CRSE at 1 000 µg/mL significantly extended the life span of worms by 18.93% without detriment to health span and fitness, as evidenced by the delayed aging-related phenotypes and increased body length and width, and reproductive output. In addition, CRSE treatment enhanced the ability of resistance to heat, oxidative, and pathogenic bacterial stress. Consistently, heat shock proteins and antioxidant enzyme-related and pathogenesis-related genes were up-regulated by CRSE treatment. Furthermore, CRSE supplementation also improved α-synuclein, 6-OHDA, and polyQ40-induced pathologies in transgenic C. elegans models of Parkinson's disease and Huntington's disease. The mechanistic study demonstrated that CRSE induced autophagy in worms, while the RNAi knockdown of 4 key autophagy-related genes, including lgg-1, bec-1, vps-34, and unc-51, remarkably abrogated the beneficial effects of CRSE on the extending of life span and health span and neuroprotection, demonstrating that CRSE exerts beneficial effects via autophagy induction in worms. Together, our current findings provide new insights into the practical application of CRS for the prevention of aging and aging-related diseases.

Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer and coronary disease pathways

Identification of the plasma proteomic changes of Coronavirus disease 2019 (COVID-19) is essential to understanding the pathophysiology of the disease and developing predictive models and novel therapeutics. We performed plasma deep proteomic profiling from 332 COVID-19 patients and 150 controls and pursued replication in an independent cohort (297 cases and 76 controls) to find potential biomarkers and causal proteins for three COVID-19 outcomes (infection, ventilation, and death). We identified and replicated 1,449 proteins associated with any of the three outcomes (841 for infection, 833 for ventilation, and 253 for death) that can be query on a web portal (https://covid.proteomics.wustl.edu/). Using those proteins and machine learning approached we created and validated specific prediction models for ventilation (AUC>0.91), death (AUC>0.95) and either outcome (AUC>0.80). These proteins were also enriched in specific biological processes, including immune and cytokine signaling (FDR [≤] 3.72x10-14), Alzheimers disease (FDR [≤] 5.46x10-10) and coronary artery disease (FDR [≤] 4.64x10-2). Mendelian randomization using pQTL as instrumental variants nominated BCAT2 and GOLM1 as a causal proteins for COVID-19. Causal gene network analyses identified 141 highly connected key proteins, of which 35 have known drug targets with FDA-approved compounds. Our findings provide distinctive prognostic biomarkers for two severe COVID-19 outcomes (ventilation and death), reveal their relationship to Alzheimers disease and coronary artery disease, and identify potential therapeutic targets for COVID-19 outcomes.