Establishment and application of a screening method for α-glucosidase inhibitors based on dual sensing and affinity chromatography.

α-Glucosidase plays a direct role in the metabolic pathways of starch and glycogen, any dysfunction in its activity could result in metabolic disease. Concurrently, this enzyme serves as a target for diverse drugs and inhibitors, contributing to the regulation of glucose metabolism in the human body. Here, an integrated analytical method was established to screen inhibitors of α-glucosidase. This step-by-step screening model was accomplished through the biosensing and affinity chromatography techniques. The newly proposed sensing program had a good linear relationship within the enzyme activity range of 0.25 U mL-1 to 1.25 U mL-1, which can quickly identify active ingredients in complex samples. Then the potential active ingredients can be captured, separated, and identified by an affinity chromatography model. The combination of the two parts was achieved by an immobilized enzyme technology and a microdevice for reaction, and the combination not only ensured efficiency and accuracy for inhibitor screening but also eliminated the occurrence of false positive results in the past. The emodin, with a notable inhibitory effect on α-glucosidase, was successfully screened from five traditional Chinese medicines using this method. The molecular docking results also demonstrated that emodin was well embedded into the active pocket of α-glucosidase. In summary, the strategy provided an efficient method for developing new enzyme inhibitors from natural products.

Bioactive Components of Areca Nut: An Overview of Their Positive Impacts Targeting Different Organs.

Areca catechu L. is a widely cultivated tropical crop in Southeast Asia, and its fruit, areca nut, has been consumed as a traditional Chinese medicinal material for more than 10,000 years, although it has recently attracted widespread attention due to potential hazards. Areca nut holds a significant position in traditional medicine in many areas and ranks first among the four southern medicines in China. Numerous bioactive compounds have been identified in areca nuts, including alkaloids, polyphenols, polysaccharides, and fatty acids, which exhibit diverse bioactive functions, such as anti-bacterial, deworming, anti-viral, anti-oxidant, anti-inflammatory, and anti-tumor effects. Furthermore, they also display beneficial impacts targeting the nervous, digestive, and endocrine systems. This review summarizes the pharmacological functions and underlying mechanisms of the bioactive ingredients in areca nut. This helps to ascertain the beneficial components of areca nut, discover its medicinal potential, and guide the utilization of the areca nut.

A homologous-targeting cGAS-STING agonist multimodally activates dendritic cells for enhanced cancer immunotherapy.

Herein, we developed a doxorubicin (Dox)-loaded and 4T1 cancer cell membrane-modified hydrogenated manganese oxide nanoparticles (mHMnO-Dox) to elicit systemic antitumor immune responses. The results revealed that mHMnO-Dox actively recognized tumor cells and then effectively delivered Dox into the cells. Upon entering tumor cells, the mHMnO-Dox underwent rapid degradation and abundant release of Mn2+ and chemotherapeutic drugs. The released Mn2+ not only catalysed a Fenton-type reaction to produce excessive reactive oxygen species (ROS) but also activated the cGAS-STING pathway to boost dendritic cell (DC) maturation. This process increased cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment into the tumor site. In addition, the released Dox could contribute to a chemotherapeutic effect, while activating DC cells and subsequently intensifying immune responses through immunogenic cell death (ICD) of tumor cells. Consequently, the mHMnO-Dox suppressed the primary and distal tumor growth and inhibited tumor relapse and metastasis, as well as prolonged the lifespan of tumor-bearing mice. Thus, the mHMnO-Dox multimodally activated DC cells to demonstrate synergistic antitumor activity, which was mediated via the activation of the cGAS-STING signalling pathway to regulate tumor microenvironment, ICD-mediated immunotherapy and ROS-mediated CDT. These findings suggest the therapeutic potential of mHMnO-Dox in cancer immunotherapy. STATEMENT OF SIGNIFICANCE: A cancer cell membrane-camouflaged hydrogenated mesoporous manganese oxide (mHMnO) has been developed as a cGAS-STING agonist and ICD inducer. The mHMnO effectively induced abundance of ROS production in cancer cells, which caused cancer cell death and then promoted DC maturation via tumour-associated antigen presentation. Meanwhile, the mHMnO significantly activated cGAS-STING pathway to facilitate DC maturation and cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment, which further enhanced tumour immune response. In addition, the combination of the mHMnO and Dox could synergistically promote tumour ICD and then multimodally induce DC maturation, achieving an enhanced CIT. Overall, this study provides a potential strategy to design novel immunologic adjuvant for enhanced CIT.

Taraxacum: A Review of Ethnopharmacology, Phytochemistry and Pharmacological Activity.

Taraxacum refers to the genus Taraxacum, which has a long history of use as a medicinal plant and is widely distributed around the world. There are over 2500 species in the genus Taraxacum recorded as medicinal plants in China, Central Asia, Europe, and the Americas. It has traditionally been used for detoxification, diuresis, liver protection, the treatment of various inflammations, antimicrobial properties, and so on. We used the most typically reported Taraxacum officinale as an example and assembled its chemical makeup, including sesquiterpene, triterpene, steroids, flavone, sugar and its derivatives, phenolic acids, fatty acids, and other compounds, which are also the material basis for its pharmacological effects. Pharmacological investigations have revealed that Taraxacum crude extracts and chemical compounds contain antimicrobial infection, anti-inflammatory, antitumor, anti-oxidative, liver protective, and blood sugar and blood lipid management properties. These findings adequately confirm the previously described traditional uses and aid in explaining its therapeutic applications.

Mechanisms by which sheep milk consumption ameliorates insulin resistance in high-fat diet-fed mice.

Sheep milk is rich in fat, protein, vitamins and minerals and is also one of the most important sources of natural bioactives. Several biopeptides in sheep milk have been reported to possess antibacterial, antiviral and anti-inflammatory properties, and they may prevent type 2 diabetes (T2D), disease and cancer. However, the precise mechanism(s) underlying the protective role of sheep milk against T2D development remains unclear. Therefore, in the current study, we investigated the effect of sheep milk on insulin resistance and glucose intolerance in high-fat diet (HFD)-fed mice, by conducting intraperitoneal glucose tolerance tests, metabolic cage studies, genomic sequencing, polymerase chain reaction, and biochemical assays. Hyperinsulinemic-euglycemic clamp-based experiments revealed that mice consuming sheep milk exhibited lower hepatic glucose production than mice in the control group. These findings further elucidate the mechanism by which dietary supplementation with sheep milk alleviates HFD-induced systemic glucose intolerance.

Single-neuron projectomes of mouse paraventricular hypothalamic nucleus oxytocin neurons reveal mutually exclusive projection patterns.

Oxytocin (OXT) plays important roles in autonomic control and behavioral modulation. However, it is unknown how the projection patterns of OXT neurons align with underlying physiological functions. Here, we present the reconstructed single-neuron, whole-brain projectomes of 264 OXT neurons of the mouse paraventricular hypothalamic nucleus (PVH) at submicron resolution. These neurons hierarchically clustered into two groups, with distinct morphological and transcriptional characteristics and mutually exclusive projection patterns. Cluster 1 (177 neurons) axons terminated exclusively in the median eminence (ME) and have few collaterals terminating within hypothalamic regions. By contrast, cluster 2 (87 neurons) sent wide-spread axons to multiple brain regions, but excluding ME. Dendritic arbors of OXT neurons also extended outside of the PVH, suggesting capability to sense signals and modulate target regions. These single-neuron resolution observations reveal distinct OXT subpopulations, provide comprehensive analysis of their morphology, and lay the structural foundation for better understanding the functional heterogeneity of OXT neurons.

Effect of Radioactive Iodine Therapy on Cancer-Specific Survival of Papillary Thyroid Cancer Tall Cell Variant.

CONTEXT: Radioactive iodine (RAI) therapy is often used as an adjuvant treatment to reduce the risk of recurrence in patients with papillary thyroid cancer (PTC). However, the effect of RAI therapy on cancer-specific survival (CSS) in patients with tall cell variant (TCV) remains controversial. OBJECTIVE: This study aimed to investigate the impact of RAI therapy on CSS in patients with TCV-PTC by analyzing data from the Surveillance, Epidemiology, and End Results database. METHODS: We identified 1281 patients with TCV-PTC in the SEER database who underwent total thyroidectomy between 2004 and 2019. Of these, 866 (67.6%) patients received RAI therapy and 415 (32.4%) did not. Propensity score matching was conducted to balance the baseline characteristics between the 2 groups. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% CI for the effect of RAI therapy on CSS. RESULTS: After propensity score matching, 373 pairs of patients were included in the analysis. The results showed no significant difference in CSS between the RAI therapy group and the non-RAI therapy group (HR 0.54, 95% CI 0.25-1.17, P = .120). Subgroup analyses indicated similar results. CONCLUSION: RAI therapy may not improve CSS in patients with TCV-PTC after total thyroidectomy. Future studies with larger sample sizes, longer follow-up periods, and better study designs are needed to confirm or refine our research findings.

Endoscopic Gasless Trans-Axillary Parathyroidectomy for Patients with Primary Hyperparathyroidism: An Observational Retrospective Study.

Objective: The objective of this study is to evaluate the efficacy and safety of the gasless trans-axillary parathyroidectomy approach for the treatment of primary hyperparathyroidism in our medical center. Methods: A retrospective analysis was conducted on patients with single parathyroid adenoma who underwent parathyroidectomy using the gasless trans-axillary approach. Results: Between June 2020 and June 2022, 41 patients (37 women and 4 men) with primary hyperparathyroidism underwent endoscopic parathyroidectomy utilizing the gasless trans-axillary approach. Postoperative levels of parathyroid hormone and calcium showed a significant decline following the procedure. No permanent damage to the recurrent laryngeal nerve was observed. The mean adenoma size was 19.2 mm, with a volume of 2.66 mL. Successful identification and resolution of hyperparathyroidism were achieved for all patients. Conclusions: Endoscopic gasless trans-axillary parathyroidectomy is a safe and viable option for patients with primary hyperparathyroidism who wish to avoid cervical scarring. The surgical outcomes were favorable, and no major complications were encountered.

Cynanchum komarovii extract for the treatment of rheumatoid arthritis by acting on synovial cells in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum komarovii (CK), the northwest Chinese region's common medicinal herb, was traditionally utilized to treat arthritis, toothache, bald sores and cholecystitis. Various forms of arthritis can be treated with CK, based on "Medicinal Plants of Chinese Desert Areas". However, the exact mechanism of action in rheumatoid arthritis (RA) is uncertain. AIM OF THE STUDY: To evaluate the in vitro and in vivo effects of CK extracts on RA and to preliminarily investigate its anti-RA mechanism of action. MATERIALS AND METHODS: The main components of CK extract were analyzed by HPLC method. The effects of CK on the proliferation and apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes (HFLS-RA) cells and the expression of apoptosis-related proteins in HFLS-RA cells were evaluated by CCK8 assay, flow cytometry and WB assay. To verify the anti-RA effect of CK extracts in vivo, a collagen-induced arthritis (CIA) rat model was established. The rats were divided into six groups: normal group, model group, CK high-dose group (1000 mg/kg, CK-H), CK medium-dose group (500 mg/kg, CK-M), CK low-dose group (250 mg/kg, CK-L) and methotrexate-positive drug group (MTX); the drug was administered continuously for 28 days. Body weight changes, joint swelling, arthritis index, bone density, ankle lesions, immune organ index, splenic lesions and inflammatory factor expression were used to evaluate the in vivo anti-RA activity of the extract. RESULTS: The findings of in vitro experiments showed that 10% CK-containing serum decreased the expression level of Bcl-2, increased the expression levels of Bax and Cleaved Caspase-3 in synovial cells, and prevented TNF-α induced aberrant proliferation and apoptotic antagonism in HFLS-RA cells. According to in vivo studies, CK extract at doses above 250 mg/kg was effective in controlling the levels of inflammatory factors, lowering the arthritis index, and improving foot swelling in CIA rats. When administered at doses up to 1000 mg/kg, CK extract significantly improved synovial lesions, increased bone density, and decreased abnormally elevated immune organ index in CIA rats. CONCLUSIONS: CK has significant anti-RA activity, and its anti-RA mechanism of action may be related to the regulation of the expression levels of apoptosis related proteins and the promotion of apoptosis in synovial cells.

Inhibitory Effect of Tea Saponin on Major Apple-Disease-Inducing Fungi.

Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.

[Electroacupuncture mitigates hyperlipidemia via improving cholesterol metabolism mediated by SCAP/SREBP-2 signaling in liver tissue in rats].

OBJECTIVE: To explore the effect of electroacupuncture (EA) on sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP)/ SREBP-2 signaling and the expressions of its downstream cholesterol metabolism related molecules 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and low-density lipoprotein receptor (LDLR) in the liver tissue in rats with hyperlipidemia (HLP), so as to reveal its mechanisms underlying improvement of HLP. METHODS: Male SD rats were randomly divided into normal control, HLP model and EA groups (n=10/group). The HLP model was established by feeding the rats with high-fat diet for 28 d. Rats in the EA group received EA stimulation (2 Hz/100 Hz, 2 mA) at "Fenglong" (ST40) and "Yinlingquan"(SP9) for 30 min, once daily for 28 d. The contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) in the serum, the activity of glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (ALT) were detected by automatic biochemical analysis. The content of TC in the liver tissue was detected using high performance liquid chromatography. The mRNA and protein expression levels of SCAP, SREBP-2, HMGCR, PCSK9 and LDLR in the liver tissue were measured by using quantitative real-time PCR and Western blot, respectively. The immunofluorescence density of liver SCAP was determined by using immunofluorescence histochemistry. RESULTS: Compared with the normal control group, the contents of liver TC, serum TC, LDL-C, the activities of AST and ALT, and the mRNA and protein expression levels of SCAP, SREBP-2, HMGCR, PCSK9 as well as SCAP immunoactivity were significantly increased (P<0.01), while the LDLR mRNA and protein levels were markedly decreased (P<0.01) in the model group. In comparison with the model group, the contents of liver TC， serum TC, LDL-C, the activities of AST and ALT and the expression of SCAP, SREBP-2, HMGCR, PCSK9 mRNAs and proteins and SCAP immunoactivity were considerably decreased in the EA group (P<0.01), while the LDLR protein level was evidently increased in the EA group (P<0.05). CONCLUSION: EA intervention can inhibit the synthesis of cholesterol in the liver and thus improve hyperlipidemia in HLP rats, which may be realized by down-regulating the protein and mRNA expressions of hepatic SCAP/SREBP-2, HMGCR and PCSK9, and up-regulating LDLR protein.

Effects of cellulose nanofibrils treatment on antioxidant properties and aroma of fresh-cut apples.

Horticultural products tend to deteriorate during postharvest storage and processing. In this study, cellulose nanofibers (CNFs) were prepared from wood to investigate the effects of CNF treatment on the storage quality, aroma composition, and antioxidant system of fresh-cut apple (Malus domestica) wedges. Compared with control treatment, CNF coating treatment significantly improved the appearance of apple wedges; reduced the decay rate of apple wedges; and delayed the decline in weight loss, firmness, and titratable acid during storage. Gas chromatography-mass spectrometry showed that CNF treatment could maintain the aroma components of apple wedges (stored for 4 days). Further investigations showed that CNF treatment increased the antioxidant system level and decreased reactive oxygen species content and membrane lipid peroxidation level of apple wedges. Overall, this study showed that CNF coating could effectively maintain the quality of fresh-cut apples during cold storage.

Predictive Value of Quantitative Duplex Ultrasound Analysis for In-stent Carotid Artery Restenosis.

Context: In-stent restenosis (ISR) is a common clinical complication after carotid artery stenting (CAS) and a major risk for a stent's fatigue life. Duplex ultrasound (DUS) is widely used for the preliminary evaluation and follow-up of extracranial carotid artery disease, but DUS stenosis grading is mainly based on the original or nonsurgical carotid artery. That grading may not be applicable to carotid artery stenosis after CAS. Objective: The study intended to investigate the predictive value of quantitative analysis of results from the DUS examination in the evaluation of ISR following CAS. Design: The research team designed a control analysis of result samples. Setting: The study took place in the Ultrasound Department at the Affiliated Yantai Yuhuangding Hospital of Qingdao University in Yantai, Shandong, China. Participants: Participants were 103 patients who underwent carotid artery stenting (CAS) between March 2017 and April 2018 at the hospital. Outcome Measures: The study used Doppler DUS and digital subtraction angiography (DSA) of the carotid artery at 12 months postoperatively to analyze the consistency of DUS and DSA in the evaluation of ISR. Taking the results of the DSA examination as the standard, the research team analyzed the differences between those results and the indicators from the DUS examination for participants with different severities of stenosis. The research team plotted the receiver operating characteristic curve (ROC) and evaluated the diagnostic efficiency of DUS indicators in the determination of restenosis, including diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Results: The DSA examination showed that stenosis severity was 0%-30% for 51 participants, 31%-50% for 27 participants, 51%-80% for 16 participants, and >80% for 9 participants. The DUS showed that stenosis severity was 0%-30% for 35 participants, 31%-50% for 38 participants, 51%-80% for 22 participants, and >80% for 8 participants. The consistency was found to be Kappa (ĸ) = 0.74. Taking the DSA as the standard, the peak systolic velocity (PSV), end diastolic velocity (EDV), peak systolic velocity of the internal carotid artery/peak systolic velocity of the common carotid artery (PSVICA/PSVCCA) significantly increased in participants with a stenosis severity of 51-80% and >80%, compared with those with a stenosis severity of <50%, and the difference was statistically significant (P < .05). The ROC curve showed that the area under curve (AUC) of the PSV predicting restenosis at a >50% severity was significantly higher than those of the EDV and PSVICA/PSVCCA (P < .05). Where the optimal cut-off-off point for the PSV was 195 cm/s, the ROC curve showed that the AUC of the PSV predicting restenosis at an >80% severity was significantly higher than that of the EDV and PSVICA/PSVCCA (P < .05). Where the optimal cut-off point for the PSV was 280 cm/s, the PSV had significantly higher diagnostic accuracy, sensitivity, and positive predictive value than the EDV and PSVICA/PSVCCA in evaluating the restenosis at a severity of >50% and >80%. Conclusions: Doppler DUS can effectively evaluate restenosis after carotid artery stenting (CAS), where a PSV ≥195 cm/s and 280 cm/s can be used as the reference indicators for >50% and >80% restenosis.

Ancient Chinese Herbal Recipe Huanglian Jie Du Decoction for Ischemic Stroke: An Overview of Current Evidence.

Ischemic stroke is a major cause of mortality and neurological morbidity worldwide. The underlying pathophysiology of ischemic stroke is highly complicated and correlates with various pathological processes, including neuroinflammation, oxidative stress injury, altered cell apoptosis and autophagy, excitotoxicity, and acidosis. The current treatment for ischemic stroke is limited to thrombolytic therapy such as recombinant tissue plasminogen activator. However, tissue plasminogen activator is limited by a very narrow therapeutic time window (<4.5 hours), selective efficacy, and hemorrhagic complication. Hence, the development of novel therapies to prevent ischemic damage to the brain is urgent. Chinese herbal medicine has a long history in treating stroke and its sequela. In the past decades, extensive studies have focused on the neuroprotective effects of Huanglian Jie Du decoction (HLJDD), an ancient and classical Chinese herbal formula that can treat a wide spectrum of disorders including ischemic stroke. In this review, the current evidence of HLJDD and its bioactive components for ischemic stroke is comprehensively reviewed, and their potential application directions in ischemic stroke management are discussed.

[Soil nematode community characteristics of alfalfa field with different growing ages in the semi-arid Loess Plateau of Central Gansu, Northwest China]. / 陇中黄土高原半干旱区不同种植年限紫花苜蓿土壤线虫群落分布特征.

To clarify the impacts of long-term alfalfa plantation on the soil nematode community, soil samples were collected from different alfalfa growing ages (2 a, 9 a, 18 a) in the semi-arid area of Loess Plateau in Central Gansu by Illumina Miseq sequencing technology. The main controlling factors affecting its community change were also explored. The results showed that soil nematode belongs to 2 classes, 7 orders, 16 families and 21 genera. Among them, Chromadorea was the dominant group (44.6%-81.4%), the relative abundance of which decreased with alfalfa growing ages. Paratylenchus, Helicotylenchus, Xiphinema, Pristionchus, Ditylenchus, Panagrolaimus, Longidorus, Aprutides, Isolaimium and Aglenchus were the special nematode species of alfalfa, among which Paratylenchus (54.1%), Helicotylenchus (23.9%) and Xiphinema (21.9%) were the dominant nematodes in 2 a, 9 a and 18 a alfalfa soil respectively. Plant-parasitic nematode was the dominant group in alfalfa soil (31.8%-67.1%), and its relative abundance decreased at first and then increased with alfalfa growing ages. Results of redundancy analysis showed that soil available phosphorus and total nitrogen were the dominant environmental factors affecting community structure of soil nematodes in the region.

High linearity silicon DC Kerr modulator enhanced by slow light for 112 Gbit/s PAM4 over 2 km single mode fiber transmission.

We demonstrate a high efficiency, high linearity and high-speed silicon Mach-Zehnder modulator based on the DC Kerr effect enhanced by slow light. The two modulation arms based on 500-µm-long grating waveguides are embedded with PN and PIN junctions, respectively. A comprehensive comparison between the two modulation arms reveals that insertion loss, bandwidth and modulation linearity are improved significantly after employing the DC Kerr effect. The complementary advantages of the slow light and the DC Kerr effect enable a modulation efficiency of 0.85 V·cm, a linearity of 115 dB·Hz2/3, and a bandwidth of 30 GHz when the group index of slow light is set to 10. Furthermore, 112 Gbit/s PAM4 transmission over 2 km standard single mode fiber (SSMF) with bit error ratio (BER) below the soft decision forward error correction (SD-FEC) threshold is also demonstrated.

RNA binding protein IGF2BP1 meditates oxidative stress-induced granulosa cell dysfunction by regulating MDM2 mRNA stability in an m6A-dependent manner.

Both genetic and microenvironmental detrimental factors are involved in ovarian dysfunction, leading to the increasing rate of involuntary childlessness in recent years. Oxidative stress (OS), which is characterized by the imbalance of redox system with redundant reactive oxygen species (ROS) overwhelming the antioxidant defense, is regarded as one of the culprits of ovarian dysfunction. OS causes damage to various types of ovarian cells including granulosa cells (GCs), jeopardizing the ovarian microenvironment, disturbing follicular development and participating in various female reproductive disorders. However, the specific molecular pathological mechanisms underlying this process have not been fully elucidated. In this study, we found that 3-nitropropionic acid (3-NP) treatment led to significant IGF2BP1 downregulation via, at least partially, inducing ROS overproduction. IGF2BP1 regulates GCs viability, proliferation, cell cycle and cellular senescence by enhancing MDM2 mRNA stability in an m6A-dependant manner. IGF2BP1 overexpression partially rescued 3-NP induced GCs damages, while ectopically expressed MDM2 alleviated both 3-NP or IGF2BP1-knockdown induced GCs dysfunction. These results reveal an epigenetic molecular mechanism underlying OS-related GCs disorders, which may help to establish a novel potential clinical marker for predicting the GCs status as well as the follicular developmental potential.

Phytochemical Composition, Antioxidant, Antibacterial, and Enzyme Inhibitory Activities of Various Organic Extracts from Apocynum hendersonii (Hook.f.) Woodson.

Apocynum hendersonii is a traditional medicinal plant used primarily as tea. It has a potential health benefit from its rich bioactive substances. This study investigated the reactivity of solvents of different polarities (ethanol, ethyl acetate, n-hexane, methanol, and water) extracts of the A. hendersonii leaf. The phytochemical composition of the extracts was evaluated using a Fourier Transform Infrared spectrophotometer (FT-IR), Gas Chromatography-Mass Spectrometry (GC-MS), UHPLC-MS, and Higher Performance Liquid Chromatography (HPLC). The result revealed the presence of medicinally important bioactive constituents, including phenols, flavonoids, and polysaccharides. Methanol extracts exhibited the highest flavonoid contents (20.11 ± 0.85 mg QE/g DW) and the second-highest in terms of phenolic (9.25 ± 0.03 mg GAE/g DW) and polysaccharide (119.66 ± 2.65 mg GE/g DW). It also had the highest antioxidant capacity with 60.30 ± 0.52% and 4.60 ± 0.02 µmol Fe2+ per g DW based on a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and ferric reducing antioxidant power (FRAP), respectively. Ethanol extract displayed the maximum antibacterial action against Gram-negative and Gram-positive bacteria and the highest inhibition activity against the enzymes tyrosinase and acetylcholinesterase, followed by methanol extract. The principal component analysis revealed a positive correlation between the constituents, bioactivities, and extracts. The overall result showed A. hendersonii as a rich natural source of antimicrobial and antioxidant bioactive compounds and may be used for future applications in pharmaceuticals and food industries.

Assessment of a cancer genomic profile test for patients with metastatic breast cancer.

Comprehensive cancer genomic profile (CGP) tests are being implemented under Japanese universal health insurance system. However, the clinical usefulness of CGP test for breast cancer patients has not been evaluated. Of the 310 patients who underwent CGP testing at our institution between November 2019 and April 2021, 35 patients with metastatic breast cancer whose treatment strategy was discussed by our molecular tumor board within the study period were investigated after exclusion of 2 cases that could not be analyzed. The turn-around time, drug accessibility, and germline identification detection were evaluated. The subtype was luminal in 20 patients (57.1%), triple-negative in 12 patients (34.3%), and luminal-HER2 in 3 patients (8.6%). Actionable gene mutations were detected in 30 patients (85.7%), and 7 patients (20.0%) were recommended for clinical trial participation, with the drug administered to 2 patients (5.7%). Three patients (8.6%) died due to disease progression before the test results were disclosed. We report the results of an initial assessment of the utility of CGP testing for patients with metastatic breast cancer under Japanese universal health insurance system. Conducting CGP tests at a more appropriate time could provide patients with greater benefit from treatments based on their specific gene mutations.