Combined healthy lifestyles and risk of depressive symptoms: A baseline survey in China.

BACKGROUND: Little evidence exists about whether a combination of healthy lifestyle factors is associated with a lower risk of depressive symptoms among Chinese population. We aimed to investigate the association between combined healthy lifestyle factors and risk of depressive symptoms. METHODS: We conducted a baseline survey from July 2021 to December 2023, including 53,642 Chinese adults from general population. A healthy lifestyle score was constructed based on six lifestyle factors (physical activity, smoking status, alcohol consumption, diet, sleep duration, and body mass index). Logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) adjusted for confounding variables. RESULTS: Each additional healthy lifestyle score was associated with a 20 % lower risk of having depressive symptoms (OR (95 % CI): 0.80 (0.78-0.81)). Compared with individuals with ≤2 healthy lifestyle factors, individuals with all the six healthy lifestyle factors had a 58 % reduced risk of having depressive symptoms (0.42 (0.37-0.47)). After stratification by gender, education and urbanization, the significant inverse association with healthy lifestyle score was stronger in women, individuals with high education, and urban residents. Besides, the significant negative association between healthy lifestyle score and depressive symptoms remained for different severity of depressive symptoms. LIMITATIONS: Given the cross-sectional nature of data, we cannot make causal inferences. CONCLUSIONS: Our study indicated that adherence to healthy lifestyle factors was associated with a reduced risk of having depressive symptoms among Chinese adults. The observed associations were modified by gender, education and urbanization. These findings warrant further verification in interventional studies.

Study on the difference and correlation between the contents and toxicity of aristolochic acid analogues in Aristolochia plants.

ETHNOPHARMACOLOGICAL RELEVANCE: The nephrotoxicity and carcinogenicity induced by traditional Chinese medicines (TCMs) containing aristolochic acids (AAs) and related compound preparations have greatly limited their clinical application. While the toxicity of AA-I and AA-II is relatively clear, there are marked differences in the toxic effects of different types of aristolochic acid analogues (AAAs). Thus, the toxicity of TCMs containing AAAs cannot be evaluated based on the toxicity of a single compound. AIM OF THE STUDY: To systematically investigate the toxicity induced by Zhushalian (ZSL), Madouling (MDL) and Tianxianteng (TXT) as representative TCMs derived from Aristolochia. MATERIALS AND METHODS: AAA contents in ZSL, MDL and TXT were determined using HPLC. Subsequently, mice were treated for 2 weeks with high (H) and low (L) dosages of TCMs containing total AAA contents of 3 mg/kg and 1.5 mg/kg, respectively. Toxicity was evaluated using biochemical and pathological examination and was based on organ indices. Correlations between AAA contents and induced toxicity were analysed using multiple methods. RESULTS: Of the total AAA content, ZSL contained mainly AA-I and AA-II (>90%, of which AA-I accounted for 49.55%). AA-I accounted for 35.45% in MDL. TXT mainly contained AA-IVa (76.84%) and other AAAs accounted for <10%. Short-term toxicity tests indicated that ZSL and high-dose MDL induced obvious renal interstitial fibrosis and gastric injury, whereas TXT (high and low dosages) caused only slight toxicity. Correlation analysis suggested that AA-I might be the critical hazard factor for toxicity. CONCLUSIONS: The toxicity of TCMs containing AAAs cannot be generalised. The toxicity of TXT is relatively low compared with those of ZSL and MDL. The toxicity of Aristolochia depends mainly on the AA-I content; therefore, control of AA-I levels in TCMs and related compound preparations is required to reduce the risk of toxicity associated with the use of Aristolochia herbs in clinical settings.

Ameliorative effect of cheqianzi decoction on hyperuricemia and kidney injury and underlying mechanism in rats.

Cheqianzi Decoction (CQD) is a Traditional Chinese Medicine (TCM) formula comprising four herbs and is recorded in the Ancient Materia Medica "Shengji Zonglu". Individually, these four herbs have been shown to reduce uric acid (UA) levels, to treat hyperuricemia (HUA), and alleviate kidney damage. However, the therapeutic efficacy of the CQD and related mechanism are not yet clear. In this study, high performance liquid chromatography (HPLC) analysis confirmed that the contents of the chemical components of the four herbal medicines were in accordance with the provisions of the Chinese Pharmacopoeia. A total of 99 potential targets were identified in the network pharmacology analysis of CQD, indicating its involvement in the regulation of inflammatory and apoptotic signaling pathways, and potential value for treating HUA and alleviating kidney injury. In vivo pharmacodynamic studies showed that compared with the Model group, significantly decreased levels of serum uric acid (SUA), serum creatinine (SCr), blood urea nitrogen (BUN) (all P < 0.05), and inflammatory factors (P < 0.01) were detected in the CQD group. Quantitative real-time PCR and Western blot analyses showed that compared with the Model group, adenosine triphosphate (ATP)-binding cassette efflux transporter G2 (ABCG2) expression in the CQD group was significantly upregulated (P < 0.01) at both the mRNA and protein levels, while mRNA expression of Caspase3 and NOD-like receptor family member 3 (NLRP3) (P < 0.05) and protein expression of NLRP3 (P < 0.01) were significantly downregulated. In conclusion, CQD promotes UA excretion by activating ABCG2, and induces inflammasome NLRP3-mediated reduction in inflammatory and apoptotic factors to achieve renal protection. Thus, our findings indicate the therapeutic potential of CQD in HUA with kidney injury.

Targeted paclitaxel prodrug nanoassemblies to improve therapeutic effects for liver cancer.

Prodrug nanoassemblies fabricated by anticancer drug conjugates exhibited more advantages in controlled drug release and bioavailability and favorable antitumor efficacy. In this paper, lactobionic acid (LA) was connected with polyethylene glycol through amido linkages, and paclitaxel was joined with polyethylene glycol by means of ester bonds to form the prodrug copolymer LA-PEG-PTX. Then, LA-PEG-PTX was automatically assembled into LA-PEG-PTX nanoparticles (LPP NPs) by dialysis. The LPP NPs had a relatively uniform size of approximately 200 nm, a negative potential (-13.68 mV), and a spherical shape under TEM. The drug loading of LPP NPs was 3.91%, which was measured by HPLC. The in vitro release profile of LPP NPs exhibited a sustained release feature. The results of the pharmacokinetic test in rats showed that LPP NPs had higher T1/2 and AUC values than the control group (free PTX) and a prolonged in vivo circulation time, thus increasing the bioavailability of PTX. Remarkably, the LPP NPs were absorbed into HepG2 cells after galactose-directed internalization and enhanced cytotoxicity. Consequently, LPP NPs displayed notable antitumor activity in Kunming mice with H22 hepatocellular carcinoma. Collectively, these findings suggested that paclitaxel prodrug-based self-assembled nanoparticles were a promising alternative for improving the bioavailability and antitumor effect of PTX.

Long-term oral administration of Asarum heterotropoides f. mandshuricum (Maxim.) Kitag. decoction and its aristolochic acid analogs do not cause renal toxicity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Asarum heterotropoides f. mandshuricum (Maxim.) Kitag. (AH) is widely used to treat influenza, COVID-19, allergic rhinitis, headache, toothache, rheumatoid arthritis, and peptic ulcer. However, its clinical use is controversial due to the concern of aristolochic acid nephropathy (AAN) caused by its component aristolochic acid analogs (AAs). AIM OF THE STUDY: The chronic toxicity of AH decoction and its main components AA IVa (AA-IVa) and aristolactam I (AL-I) was evaluated in mice. MATERIALS AND METHODS: AAs contents in AH were quantitated by liquid chromatography-mass spectrometry. A parallel design was employed to examine the potential chronic toxicity of AH decoction at doses equivalent to 0.5, 1.6, and 5.0 g/kg AH (approximately 10-100 times the clinical doses for humans) and its major AA components at doses equivalent to that in 5.0 g/kg AH to mice after consecutive daily oral administration for 12 and 24 weeks, and at 32 weeks after withdrawal for 8 weeks. RESULTS: AH crude herb contained 2.18 µg/g of AA-I, 48.49 µg/g of AA-IVa, and 14.0 µg/g of AL-I. AH decoction contained 5.45 µg/g of AA-IVa and 2.71 µg/g of AL-I. None of AA-II and AA-IIIa were detected in AH. After long-term administration of AH decoction and its major components AA-IVa and AL-I, mice showed no signs of illness or body weight changes. In addition, biochemical and pathohistological examinations showed that long-term administration of AH decoction and its major components AA-IVa and AL-I did not alter 1) serum levels of glutamic-pyruvic transaminase, glutamic oxalacetic transaminase, alkaline phosphatase, creatinine, and urea nitrogen, 2) renal tissue mRNA expression of kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin, and 3) pathological morphology in the mouse liver, kidney, stomach, and bladder. CONCLUSIONS: AH has no obvious toxicity to mice and is relatively safe when it is used in the form of decoction. AA-IVa and AL-I, the two major AAs in AH, are not toxic to mice at the dose equivalent to that in the high dose of AH decoction. Considering the limited toxicological data on AH, we recommend that AH decoction medication should not overdose and the duration should not be too long.

Penilloic acid is the chief culprit involved in non-IgE mediated, immediate penicillin-induced hypersensitivity reactions in mice.

Metabolites/impurities (MIs) of penicillin are normally considered to be the main substances inducing immediate hypersensitivity reactions in penicillin treatment. Our previous research found that penicillin can cause non-allergic hypersensitivity reactions (NAHRs) by directly triggering vascular hyperpermeability and exudative inflammation. However, the chief culprits and underlying mechanisms involved in penicillin-induced NAHRs have not yet been fully elucidated. In this study, we used a combination of approaches including a mouse non-allergic hypersensitivity reaction model, UPLC-MS/MS analyses of arachidonic acid metabolites (AAMs), immunoblotting technique, and molecular docking, etc to investigate the culprits involved in penicillin-induced hypersensitivity reactions. We found penilloic acid, one of the main MIs of penicillin, could trigger NAHRs via inducing increased vascular permeability, while the other MIs did no exhibit similar effect. Penilloic acid-induced reactions were not IgE-dependent. Significantly increased arachidonic acids and cascade metabolites in lungs, and activation of RhoA/ROCK signaling pathway in the ears and lungs of mice were noticed after once administration of penilloic acid. This study revealed that penilloic acid was the chief culprit involved in penicillin-induced immediate NAHRs in mice, which mainly associated with direct stimulation of vascular hyperpermeability and exudative inflammation. The activations of AAMs and RhoA/ROCK signaling pathway played important roles in these reactions.

Ultra-performance chromatography-electrospray tandem mass spectrometry analysis of bile acid profiles in the enterohepatic circulation following geniposide and acetaminophen-induced liver injury.

Bile acids (BAs) play an important role in pre-diagnosing drug-induced liver injury (DILI). However, in clinical practice, different types of liver injury are characterized by different pathogeneses and pathological manifestations. Therefore, whether BAs can be used as biomarkers across different DILIs remains unclear. In this study, an ultra-performance chromatography-mass spectrometry (MS)/MS-based technique was developed for the simultaneous quantitative analysis of 31 BAs in the serum, liver, feces, urine, and intestinal contents of rats treated with acetaminophen (APAP) and geniposide to induce liver injury. The total extraction recovery for representative analytes ranged between 80.60% and 99.23% in the serum, urine, liver, feces, and intestinal contents. The correlation coefficients for all standard curves of the different matrices were at least 0.99. Validation of the BA analytical method including selectivity, residue, lower limit of quantification, accuracy, precision, matrix effect, and stability conformed with the biospecimen quality control standards of the Chinese Pharmacopoeia (version 2020). Serum biochemical and pathohistological analyses revealed APAP- and geniposide-induced hepatocellular and cholestatic DILI, respectively, with different effects on BA profiles in the enterohepatic circulation. Metabolomics further revealed that the trends in BA changes in the serum, feces, urine, and intestinal tissues were consistent between the geniposide- and APAP-treated groups. However, in the liver, the total BAs (TBA) concentration increased by 1.70 fold in the geniposide group but decreased by 43% in the APAP group compared with the control group. Multivariate analysis revealed differentially expressed BAs, including TCA, CA, and GCA, which are potential biomarkers for DILI, in the serum, liver, and urine following treatment with geniposide. Interestingly, the differentially expressed BAs in the APAP group were similar to those in the control group. Additionally, the magnitude of changes in the TBA in the urine (3.3 fold and 15.5 fold in the APAP and geniposide groups, respectively) was higher than that in the blood (290 fold and 640 fold in the APAP and geniposide groups, respectively). However, given the BA profiles after geniposide- and APAP-induced liver injury, BAs were found to be more suitable as biomarkers for diagnosing cholestatic liver injury. Overall, the BA assay developed in this study is rapid, simple, accurate, validated, sensitive, and suitable for analyzing the levels and distribution of BAs in various parts of the enterohepatic circulation.

A review of the ethnopharmacology, phytochemistry, pharmacology and toxicology of Fructus Gardeniae (Zhi-zi).

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Gardeniae (FG) is the dried fruit of Gardenia jasminoides Ellis (GjE), which belongs to the family Rubiaceae. FG has a long history of use as a herb, and was originally recorded in Sheng Nong's herbal classic. FG has also been widely used as both medicine and food. AIM OF STUDY: This review aimed to provide a systematic and comprehensive analysis of the current research progress of FG in terms of ethnopharmacology, phytochemistry, pharmacology and toxicity, to provide new insights and extensive field of view for subsequent studies. METHODS: Scientific databases, including CNKI, VIP (Chinese literature), PubMed, Science Direct, Elsevier and Google Scholar (English literatures) were searched to gather data about FG and its main active ingredients such as geniposide and genipin (only regarding toxicity). RESULTS: Many chemical constituents have been identified from the fruit of GjE, including iridoids, terpenoids, flavonoids, organic acids, volatile oils and others. The constituents of different parts of FG and processed FG are different from those of whole FG. FG extract and its main active constituents have been reported to have pharmacological properties such as hepatoprotective, choleretic, anti-inflammatory, antioxidant, neuroprotective, anti-diabetic, anti-apoptotic and antitumor activities. However, an increasing number of studies have shown that FG induces multiple organ injury, especially causing hepatotoxicity and nephrotoxicity, which could increase the risk during clinical use. The available literature shows that geniposide, a major active component of FG and a critical marker for its quality, is associated with the pharmacology and toxicity of FG. CONCLUSION: Although a large number of studies examining FG have been published, issues remain. In the aspect of FG's pharmacology, the traditional efficacy and modern pharmacological effects of FG should be combined, which to broadens clinical application prospects. In addition, few studies have assessed the toxicity of FG. Toxicity assessment of FG should tackle various aspects, including compatibility, processing and the symptom-based prescription theory, in addition to over-dosage or long-term use, for a reasonable clinical use.

Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines.

Asarum (Xixin), which contains analogues of aristolochic acid (AA), is the only species of the genus Aristolochia included in the Chinese Pharmacopoeia 2020. However, the contents and nephrotoxic effects of AA analogs in Asarum (Xixin) and its formulations have not been clarified. An automatic, effective solid phase extraction process and UPLC-MS/MS method were established for the pretreatment and quantitative detection of AA analogues in commercially available traditional Chinese patent medicines. The cytotoxicity and DNA damage induced by five analogues of AA were evaluated by CCK8 using human kidney cells (HK-2) and comet assays. HPLC was used to detect the analogues of AA in Asarum heterotropoides F. Schmidt (Xixin). The results showed that the contents of AA I, AA II, and AA IIIa were below the detection limit, while AA IVa and AL I presented relatively high contents of Asarum heterotropoides F. Schmidt (Xixin), within the range of 66.50-121.03 µg/g and 19.73-43.75 µg/g, respectively. The levels of AA analogues were in the nanogram-per-gram level in the main traditional Chinese patent medicines. AA I and AL I exhibited relatively high cytotoxicity at 48 h in CCK8 assays, while AA II, AA IIIa, and AA IVa showed weak cytotoxicity even at 800-1,000 µM. AA I induced significant pathological alterations and direct DNA damage at 40 mg/kg and 20 mg/kg, respectively. No distinct nephrotoxicity or hepatotoxicity was observed in mice treated with AA II, AA IIIa, AA IVa, or AL I at 40 mg/kg in this study. Consumption of Asarum heterotropoides F. Schmidt (Xixin) with controlled doses and periods is relatively safe as the contents of AA analogues in Asarum heterotropoides F. Schmidt (Xixin) and its formulations were far below those causing acute toxicity in this study. But, the long-term toxicity of Asarum heterotropoides F. Schmidt (Xixin) still needs further study.

[Effect of scaling and root planing on serum C-reactive protein levels in patients with moderate to severe chronic periodontitis: a systematic review and Meta-analysis].

OBJECTIVE: To evaluate the effect of scaling and root planing (SRP) on serum C-reactive protein (CRP) levels in patients with moderate to severe chronic periodontitis. METHODS: We searched the PubMed, Web of Science, EMBASE, Cochrane, CNKI, Wanfang, and VIP databases from the inception to July 8th, 2019. Two reviewers independently screened literature, extracted data, and evaluated the bias risk of included studies. Then, a meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 13 randomized controlled clinical trials and 12 prospective clinical trials were included. Meta-analysis showed that serum CRP levels decreased at 2 and 3 months after SRP (P<0.05), and no significant difference in serum CRP levels was found at 6 months (P=0.49). CONCLUSIONS: SRP can reduce serum CRP levels in systematically healthy patients with moderate to severe chronic periodontitis at 2 and 3 months after SRP.

Impact of SNP-SNP interaction among ABCB1, ARRB2, DRD1 and OPRD1 on methadone dosage requirement in Han Chinese patients.

AIM: To evaluate the potential association of the genetic polymorphisms in ABCB1, ARRB2, DRD1 and OPRD1 genes with methadone dosage requirement among Han Chinese opioid-dependent patients. MATERIALS & METHODS: Eight SNPs in ABCB1, ARRB2, DRD1 and OPRD1 genes were selected and genotyped using Sequenom MassARRAY platform among 257 methadone maintenance treatment patients. The required information about stable methadone dose, urine analysis for opioid and socio-demographic characteristics was collected. Generalized multifactor dimensionality reduction method was performed to analyze the SNP-SNP interaction. RESULTS: We found that patients carrying the rs529520TG genotype of OPRD1 probably required higher methadone treatment dosage. A 3-locus SNP-SNP interaction pattern (rs1128503 in ABCB1, rs529520 in OPRD1 and rs1045280 in ARRB2) was significantly associated with the methadone dosage requirement (p = 0.029). CONCLUSION: Our results suggested that specific OPRD1 variants and interaction among polymorphisms in ABCB1, OPRD1 and ARRB2 genes contributes to methadone dosage requirement in Han Chinese opioid-dependent patients.