Cathepsins and cancer risk: a Mendelian randomization study.

Background: Previous observational epidemiological studies reported an association between cathepsins and cancer, however, a causal relationship is uncertain. This study evaluated the causal relationship between cathepsins and cancer using Mendelian randomization (MR) analysis. Methods: We used publicly available genome-wide association study (GWAS) data for bidirectional MR analysis. Inverse variance weighting (IVW) was used as the primary MR method of MR analysis. Results: After correction for the False Discovery Rate (FDR), two cathepsins were found to be significantly associated with cancer risk: cathepsin H (CTSH) levels increased the risk of lung cancer (OR = 1.070, 95% CI = 1.027-1.114, P = 0.001, PFDR = 0.009), and CTSH levels decreased the risk of basal cell carcinoma (OR = 0.947, 95% CI = 0.919-0.975, P = 0.0002, P FDR = 0.002). In addition, there was no statistically significant effect of the 20 cancers on the nine cathepsins. Some unadjusted low P-value phenotypes are worth mentioning, including a positive correlation between cathepsin O (CTSO) and breast cancer (OR = 1.012, 95% CI = 1.001-1.025, P = 0.041), cathepsin S (CTSS) and pharyngeal cancer (OR = 1.017, 95% CI = 1.001-1.034, P = 0.043), and CTSS and endometrial cancer (OR = 1.055, 95% CI = 1.012-1.101, P = 0.012); and there was a negative correlation between cathepsin Z and ovarian cancer (CTSZ) (OR = 0.970, 95% CI = 0.949-0.991, P = 0.006), CTSS and prostate cancer (OR = 0.947, 95% CI = 0.902-0.944, P = 0.028), and cathepsin E (CTSE) and pancreatic cancer (OR = 0.963, 95% CI = 0.938-0.990, P = 0.006). Conclusion: Our MR analyses showed a causal relationship between cathepsins and cancers and may help provide new insights for further mechanistic and clinical studies of cathepsin-mediated cancer.

Antidepressant effect of licorice total flavonoids and liquiritin: A review.

With the development of society and changes in lifestyle, major depressive disorder (MDD) has become a significant disease that plagues many people. Licorice, an excellent natural medicine with a long history of cultivation and application, is found in classical antidepressant prescriptions such as Chaihu Shugan Powder, Ganmai Dazao Decoction, Suanzaoren Decoction, etc. Licorice mainly contains triterpenoids and flavonoids, among which licorice total flavonoids (LF) and liquiritin are the main active components with good antidepressant effects. The pharmacological effects of licorice have been extensively investigated in current studies. However, a review of the antidepressant effects of LF and liquiritin has not been conducted. This article reviews the antidepressant effects of LF and liquiritin, including the biological characteristics of licorice and the pharmacological mechanism of LF and liquiritin in treating MDD. Studies have shown that LF and liquiritin can exert their antidepressant effects by improving depressive behavior, regulating endocrine and hypothalamic-pituitary-adrenal (HPA) axis function, affecting the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling pathway, enhancing synaptic plasticity, increasing monoamine neurotransmitter levels, protecting nerve cells, reducing inflammation, preventing apoptosis, reducing oxidation and other ways. This lays a theoretical foundation for the development of antidepressant drugs.

Corrigendum: A biophoton method for identifying the quality states of fresh Chinese herbs.

[This corrects the article DOI: 10.3389/fphar.2023.1140117.].

A biophoton method for identifying the quality states of fresh Chinese herbs.

Introduction: The quality of Chinese herbs is the basis for ensuring their safety and efficacy. However, the quality evaluation system is imperfect. In particular, there is a lack of quality evaluation methods for fresh Chinese herbs during growth. The biophoton is a common phenomenon and provides complete information about the interior of the living system, which is consistent with the holistic concept of traditional Chinese medicine. Therefore, we aim to correlate the biophoton characteristics with the quality states to find the biophoton parameters that can characterize the quality states of fresh Chinese herbs. Methods: The biophoton characteristics of motherwort and safflower were measured and characterized by the counts per second (CPS) in the steady state and the initial intensity (I0) and coherent time (T) of delayed luminescence. The active ingredient content was measured by ultra-high-performance liquid chromatography (UPLC). The pigment content of motherwort leaves was measured by UV spectrophotometry. The t-test and correlation analysis were performed on the experimental results. Results: The CPS and I0 of motherwort and I0 of safflower showed a significant downward trend during the growth process, and their active ingredient content showed a trend that increased and then decreased. The CPS, I0, and the content of active ingredients and pigments in a healthy state were significantly higher than those in a poor state, while T showed the opposite results. The CPS and I0 were all significantly and positively correlated with the content of active ingredients and pigments, while the T of motherwort showed the opposite results. Conclusion: It is feasible to identify the quality states of fresh Chinese herbs by using their biophoton characteristics. Both CPS and I0 have better correlations with the quality states and can be considered characteristic parameters of the quality of fresh Chinese herbs.

The application and trend of ultra-weak photon emission in biology and medicine.

Ultra-weak bioluminescence, also known as ultra-weak photon emission (UPE), is one of the functional characteristics of biological organisms, characterized by specialized, low-energy level luminescence. Researchers have extensively studied UPE for decades, and the mechanisms by which UPE is generated and its properties have been extensively investigated. However, there has been a gradual shift in research focus on UPE in recent years toward exploring its application value. To better understand the application and trend of UPE in biology and medicine, we have conducted a review of relevant articles in recent years. Among the several topics covered in this review is UPE research in biology and medicine (including traditional Chinese medicine), primarily focused on UPE as a promising non-invasive tool for diagnosis and oxidative metabolism monitoring as well as a potential tool for traditional Chinese medicine research.

The modulation of gut microbiota by herbal medicine to alleviate diabetic kidney disease - A review.

The treatment of diabetic kidney disease (DKD) has been the key concern of the medical community. Herbal medicine has been reported to alleviate intestinal dysbiosis, promote the excretion of toxic metabolites, and reduce the secretion of uremic toxins. However, the current understanding of the modulation of the gut microbiota by herbal medicine to delay the progression of DKD is still insufficient. Consequently, we reviewed the knowledge based on peer-reviewed English-language journals regarding regulating gut microbiota by herbal medicines in DKD. It was found that herbal medicine or their natural extracts may have the following effects: modulating the composition of intestinal flora, particularly Akkermansia, Lactobacillus, and Bacteroidetes, as well as adjusting the F/B ratio; increasing the production of SCFAs and restoring the intestinal barrier; reducing the concentration of uremic toxins (p-cresol sulfate, indole sulfate, TMAO); inhibiting inflammation and oxidative stress.

Rhein for treating diabetes mellitus: A pharmacological and mechanistic overview.

With the extension of life expectancy and changes in lifestyle, the prevalence of diabetes mellitus is increasing worldwide. Rheum palmatum L. a natural botanical medicine, has been used for thousands of years to prevent and treat diabetes mellitus in Eastern countries. Rhein, the main active component of rhubarb, is a 1, 8-dihydroxy anthraquinone derivative. Previous studies have extensively explored the clinical application of rhein. However, a comprehensive review of the antidiabetic effects of rhein has not been conducted. This review summarizes studies published over the past decade on the antidiabetic effects of rhein, covering the biological characteristics of Rheum palmatum L. and the pharmacological effects and pharmacokinetic characteristics of rhein. The review demonstrates that rhein can prevent and treat diabetes mellitus by ameliorating insulin resistance, possess anti-inflammatory and anti-oxidative stress properties, and protect islet cells, thus providing a theoretical basis for the application of rhein as an antidiabetic agent.

The Effect of Selenium on CYP450 Isoform Activity and Expression in Pigs.

Selenium is an essential nutrient in diets; however, the effects of selenium on enzyme metabolic activation are not currently clear. Cytochromes P450 (CYP450) are major phase I metabolic enzymes involved in the biotransformation of xenobiotics and endogenous compounds to form electrophilic reactive metabolites. To investigate the effect of selenium on CYP450 isoform activity, the Landrace pigs were divided into three groups: the control group (containing Se 0.15 mg/kg), the Se-deficient group (Se 0.03 mg/kg), and the Se-supply group (Se 0.35 mg/kg). After 1 week of administration, a mixed solution (20 mg/kg of dextromethorphan, phenacetin, chlorzoxazone, and 10 mg/kg of testosterone in a CMC-Na solution) was intravenously injected into all pigs. The mixed solution content and pharmacokinetic parameters were assayed by HPLC and DAS, respectively. To investigate the effect of selenium on CYP450 isoform expression, RNA-Seq analysis, Western boltting, and qPCR were used. Results showed that Se-supply group significantly increased the activity and expression of CYP1A2 and CYP2D25, and decreased CYP3A29. Se-deficient group decreased the activity of CYP1A2, CYP2D25, and CYP2E1. These results demonstrated that selenium content affecting the activity or expression of the CYP450 isoform may lead to a food-drug interaction.

The Essential Oils and Eucalyptol From Artemisia vulgaris L. Prevent Acetaminophen-Induced Liver Injury by Activating Nrf2-Keap1 and Enhancing APAP Clearance Through Non-Toxic Metabolic Pathway.

Artemisia has long been used in traditional medicine and as a food source for different functions in eastern Asia. Artemisia vulgaris L. (AV) is a species of the genus Artemisia. Essential oils (EOs) were extracted from AV by subcritical butane extraction. EO contents were detected by electronic nose and headspace solid-phase microextraction coupled with gas chromatography (HS-SPME-GC-MS). To investigate the hepatoprotective effects, mice subjected to liver injury were treated intragastrically with EOs or eucalyptol for 3 days. Acetaminophen (APAP) alone caused severe liver injury characterized by significantly increased serum AST and ALT levels, ROS and hepatic malondialdehyde (MDA), as well as liver superoxide dismutase (SOD) and catalase (CAT) depletions. EOs significantly attenuated APAP-induced liver damages. Further study confirmed that eucalyptol is an inhibitor of Keap1, the affinity K D of eucalyptol and Keap1 was 1.42 × 10-5, which increased the Nrf2 translocation from the cytoplasm into the mitochondria. The activated Nrf2 increased the mRNA expression of uridine diphosphate glucuronosyltransferases (UGTs) and sulfotransferases (SULTs), also inhibiting CYP2E1 activities. Thus, the activated Nrf2 suppressed toxic intermediate formation, promoting APAP hepatic non-toxicity, whereby APAP was metabolized into APAP-gluc and APAP-sulf. Collectively, APAP non-toxic metabolism was accelerated by eucalyptol in protecting the liver against APAP-induced injury, indicating eucalyptol or EOs from AV potentials as a natural source of hepatoprotective agent.

MicroRNA-27a participates in the pathological process of depression in rats by regulating VEGFA.

The present study aimed to determine the expression of vascular endothelial growth factor A (VEGFA) and microRNA (miRNA/miR)-27a in hippocampal tissues, and serum from a depression model of rats. In addition, the present study aimed to understand the mechanism of regulation of miR-27a in depression. A total of 40 male rats were selected, and divided into the control and depression model groups. The rats in the model group were subjected to 14 types of stimulations to model depression. By determining the body weight, syrup consumption rate and open field test score, the extent of depression in the rats was evaluated. Quantitative-polymerase chain reaction was used to determine the expression of VEGFA mRNA and miR-27a in hippocampal tissues, and serum. ELISA was used to measure the content of VEGFA protein in serum, while western blotting was employed to determine the expression of VEGFA protein in hippocampal tissues. A dual luciferase assay was carried out to identify the interactions between VEGFA mRNA and miR-27a. The rats in the depression model group showed depression symptoms and the depression model was successfully constructed. Rats with depression had lower VEGFA mRNA and protein expression in the hippocampus, and peripheral blood compared with the control group. Rats in the depression model group had reduced levels of miR-27a in the hippocampus and peripheral blood, which may be associated with the levels of VEGFA. miR-27a was able to bind with the 3'-untranslated region of VEGFA mRNA to regulate its expression. The present study demonstrated that miR-27a expression in hippocampal tissues and blood from rats with depression is upregulated, while the expression of VEGFA mRNA and protein is downregulated. miR-27a may participate in the pathological process of depression in rats by regulating VEGFA.