AI-assisted literature exploration of innovative Chinese medicine formulas.

Objective: Our study provides an innovative approach to exploring herbal formulas that contribute to the promotion of sustainability and biodiversity conservation. We employ data mining, integrating keyword extraction, association rules, and LSTM-based generative models to analyze classical Traditional Chinese Medicine (TCM) texts. We systematically decode classical Chinese medical literature, conduct statistical analyses, and link these historical texts with modern pharmacogenomic references to explore potential alternatives. Methods: We present a novel iterative keyword extraction approach for discerning diverse herbs in historical TCM texts from the Pu-Ji Fang copies. Utilizing association rules, we uncover previously unexplored herb pairs. To bridge classical TCM herbal pairs with modern genetic relationships, we conduct gene-herb searches in PubMed and statistically validate this genetic literature as supporting evidence. We have expanded on the present work by developing a generative language model for suggesting innovative TCM formulations based on textual herb combinations. Results: We collected associations with 7,664 PubMed cross-search entries for gene-herb and 934 for Shenqifuzheng Injection as a positive control. We analyzed 16,384 keyword combinations from Pu-Ji Fang's 426 volumes, employing statistical methods to probe gene-herb associations, focusing on examining differences among the target genes and Pu-Ji Fang herbs. Conclusion: Analyzing Pu-Ji Fang reveals a historical focus on flavor over medicinal aspects in TCM. We extend our work on developing a generative model from classical textual keywords to rapidly produces novel herbal compositions or TCM formulations. This integrated approach enhances our comprehension of TCM by merging ancient text analysis, modern genetic research, and generative modeling.

Steroidal Saponins from Water Eggplant (Fruits of Solanum torvum) Exhibit Anti-Epileptic Activity against Pentylenetetrazole-Induced Seizure Model in Zebrafish.

The fruits of Solanum torvum Swartz, a wild relative of eggplant, are consumed as a wild vegetable in tropical regions of Africa, Asia, and South America. In traditional Chinese medicine, it is believed to have anti-inflammatory and sedative effects. In the Philippines, water decoction is used to treat hyperactivity disorder. Twenty-two steroidal saponins were isolated and purified from the fruits grown in Yunnan, China, including six new compounds: torvosides U-Z (1-6). During drying and cooking, the saponins may undergo transformation, resulting in small amounts of sapogenins. These transformations can include dehydration of hydroxyl groups at position C22, formation of double bonds at position 20, 22 or 22, 23, and even formation of peroxide products. Saponin compounds torvoside X (4), torvoside Y (5), torvoside A (7), and (25S)-3-oxo-5α-spirostan-6α-yl-O-ß-d-xylopyranoside (20), which are glycosylated at C-6, showed certain anti-epileptic activity in a pentylenetetrazole-induced zebrafish seizure model. No antiproliferative activity was detected when tested on the cancer cell line HepG2, and no hepatotoxic effect was noted on normal liver cell line LO2.

A novel DDIT3 activator dehydroevodiamine effectively inhibits tumor growth and tumor cell stemness in pancreatic cancer.

BACKGROUND: The existence of pancreatic cancer stem cells (PCSCs) results in limited survival benefits from current treatment options. There is a scarcity of effective agents for treating pancreatic cancer patients. Dehydroevodiamine (DeHE), a quinazoline alkaloid isolated from the traditional Chinese herb Evodiae fructus, exhibited potent inhibition of pancreatic ductal adenocarcinoma (PDAC) cell proliferation and tumor growth both in vitro and in vivo. METHODS: The cytotoxic effect of DeHE on PDAC cells was assessed using CCK-8 and colony formation assays. The antitumor efficacy of DeHE were appraised in human PANC-1 xenograft mouse model. Sphere formation assay and flow cytometry were employed to quantify the tumor stemness. RNA-Seq analysis, drug affinity responsive target stability assay (DARTS), and RNA interference transfection were conducted to elucidate potential signaling pathways. Western blotting and immunohistochemistry were utilized to assess protein expression levels. RESULTS: DeHE effectively inhibited PDAC cell proliferation and tumor growth in vitro and in vivo, and exhibited a better safety profile compared to the clinical drug gemcitabine (GEM). DeHE inhibited PCSCs, as evidenced by its suppression of self-renewal capabilities of PCSCs, reduced the proportion of ALDH+ cells and downregulated stemness-associated proteins (Nanog, Sox-2, and Oct-4) both in vitro and in vivo. Furthermore, there is potential involvement of DDIT3 and its downstream DDIT3/TRIB3/AKT/mTOR pathway in the suppression of stemness characteristics within DeHE-treated PDAC cells. Additionally, results from the DARTS assay indicated that DeHE interacts with DDIT3, safeguarding it against degradation mediated by pronase. Notably, the inhibitory capabilities of DeHE on PDAC cell proliferation and tumor stemness were partially restored by siDDIT3 or the AKT activator SC-79. CONCLUSION: In summary, our study has identified DeHE, a novel antitumor natural product, as an activator of DDIT3 with the ability to suppress the AKT/mTOR pathway. This pathway is intricately linked to tumor cell proliferation and stemness characteristics in PDAC. These findings suggest that DeHE holds potential as a promising candidate for the development of innovative anticancer therapeutics.

Biosynthesis of novel desferrioxamine derivatives requires unprecedented crosstalk between separate NRPS-independent siderophore pathways.

Iron is essential to many biological processes but its poor solubility in aerobic environments restricts its bioavailability. To overcome this limitation, bacteria have evolved a variety of strategies, including the production and secretion of iron-chelating siderophores. Here, we describe the discovery of four series of siderophores from Streptomyces ambofaciens ATCC23877, three of which are unprecedented. MS/MS-based molecular networking revealed that one of these series corresponds to acylated desferrioxamines (acyl-DFOs) recently identified from S. coelicolor. The remaining sets include tetra- and penta-hydroxamate acyl-DFO derivatives, all of which incorporate a previously undescribed building block. Stable isotope labeling and gene deletion experiments provide evidence that biosynthesis of the acyl-DFO congeners requires unprecedented crosstalk between two separate non-ribosomal peptide synthetase (NRPS)-independent siderophore (NIS) pathways in the producing organism. Although the biological role(s) of these new derivatives remain to be elucidated, they may confer advantages in terms of metal chelation in the competitive soil environment due to the additional bidentate hydroxamic functional groups. The metabolites may also find application in various fields including biotechnology, bioremediation, and immuno-PET imaging.IMPORTANCEIron-chelating siderophores play important roles for their bacterial producers in the environment, but they have also found application in human medicine both in iron chelation therapy to prevent iron overload and in diagnostic imaging, as well as in biotechnology, including as agents for biocontrol of pathogens and bioremediation. In this study, we report the discovery of three novel series of related siderophores, whose biosynthesis depends on the interplay between two NRPS-independent (NIS) pathways in the producing organism S. ambofaciens-the first example to our knowledge of such functional cross-talk. We further reveal that two of these series correspond to acyl-desferrioxamines which incorporate four or five hydroxamate units. Although the biological importance of these novel derivatives is unknown, the increased chelating capacity of these metabolites may find utility in diagnostic imaging (for instance, 89Zr-based immuno-PET imaging) and other applications of metal chelators.

Sesquiterpenoids from aged Artemisia argyi and their 3D-QSAR for anti-HBV activity.

Artemisia argyi Levl. Et Vant, commonly known as "Chinese Mugwort," has been utilized in traditional Chinese medicine and cuisine for centuries. Aged Chinese Mugwort has been uncovered to possess superior quality and safety, and its ethyl acetate extract has been found to exhibit anti-hepatitis B virus (HBV) activity. In this study, twenty-five sesquiterpenoids were isolated and characterized from three-year-aged A. argyi. Among them, 14 previously undescribed sesquiterpenoids (1-14), featuring double bond oxidation or ring opening. It is hypothesized that during the aging process, sesquiterpenes undergo oxidative transformation of their double bonds to form alcohols due to external factors and inherent properties. The anti-HBV activity and cytotoxicity of all compounds were assessed in vitro using HepG 2.2.15 cells, and their structure-activity relationships were analyzed through three-dimensional quantitative structure-activity relationship (3D-QASR) techniques. The α-methylene-γ-lactone sesquiterpenoid derivatives were discovered to have potent inhibitory activity against HBV. This research may broaden the potential applications of Chinese Mugwort and offer further guidance for its development and utilization as functional food or traditional Chinese medicine.

tVNS in Stroke: A Narrative Review on the Current State and the Future.

Ischemic stroke is a leading cause of disability and there is a paucity of therapeutic strategies that promote functional recovery after stroke. Transcutaneous vagus nerve stimulation (tVNS) has shown promising evidence as a tool to reduce infarct size in animal models of hyperacute stroke. In chronic stroke, tVNS paired with limb movements has been shown to enhance neurological recovery. In this review, we summarize the current evidence for tVNS in preclinical models and clinical trials in humans. We highlight the mechanistic pathways involved in the beneficial effects of tVNS. We critically evaluate the current gaps in knowledge and recommend the key areas of research required to translate tVNS into clinical practice in acute and chronic stroke.

Therapeutic Effects of Plant Extracts of Anoectochilus roxburghii on Side Effects of Chemotherapy in BALB/c Breast Cancer Mice.

Breast cancer is the most common cancer in women, and chemotherapy is an effective treatment. However, chemotherapy often causes adverse side effects such as cardiotoxicity, myelosuppression, immunodeficiency, and osteoporosis. Our study focused on the alleviating effects of Anoectochilus roxburghii extracts (AREs) on the adverse side effects of chemotherapy in mice with breast cancer. We individually evaluated the antioxidant capacity and cytotoxicity of the AREs using DPPH and MTT assays. We also examined the effects of the AREs on intracellular F-actin, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) of 4T1 cancer cells before and after doxorubicin (DOX) treatment. Our results showed that ARE treatment enhanced the effects of DOX chemotherapy by promoting cell morphology damage, oxidative stress, and ROS generation, as well as by reducing MMP in the 4T1 breast cancer cells. By using BALB/c mice with breast cancer with DOX treatment, our results showed that the DOX treatment reduced body weight, blood pressure, and heart rate and induced myelosuppression, immunodeficiency, cardiotoxicity, and osteoporosis. After oral ARE treatment of BALB/c mice with breast cancer, the chemotherapeutic effects of DOX were enhanced, and the adverse side effects of DOX chemotherapy were alleviated. Based on the above results, we suggest that AREs can be used as an adjuvant reliever to DOX chemotherapy in BALB/c mice with breast cancer.

Mechanism of Yiqi Huoxue Huatan recipe in the treatment of coronary atherosclerotic disease through network pharmacology and experiments.

In recent years, with population aging and economic development, morbidity and mortality of atherosclerotic cardiovascular disease associated with atherosclerosis (AS) have gradually increased. In this study, a combination of network pharmacology and experimental verification was used to systematically explore the action mechanism of Yiqi Huoxue Huatan Recipe (YHHR) in the treatment of coronary atherosclerotic heart disease (CAD). We searched and screened the active ingredients of Coptis chinensis, Astragalus membranaceus, Salvia miltiorrhiza, and Hirudo. We also searched multiple databases for related target genes corresponding to the compounds and CAD. STRING was used to construct the protein-protein interaction (PPI) network of genes. Metascape was used to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common targets to analyze the main pathways, and finally, the molecular docking and main possible pathways were verified by experimental studies. Firstly, a total of 1480 predicted target points were obtained through the Swiss Target Prediction database. After screening, merging, and deleting duplicate values, a total of 768 targets were obtained. Secondly, "Coronary atherosclerotic heart disease" was searched in databases such as the OMIM, GeneCards, and TTD. 1844 disease-related targets were obtained. Among PPI network diagram of YHHR-CAD, SRC had the highest degree value, followed by AKT1, TP53, hsp90aa1 and mapk3. The KEGG pathway bubble diagram was drawn using Chiplot, the Signal pathways such as NF kappa B signaling pathway, Lipid and AS, and Apelin signaling pathway are closely related to the occurrence of CAD. The PCR and Western blot methods were used to detect the expression of NF-κB p65. When compared with that in the model group, the expression of NF-κB p65mRNA decreased in the low-concentration YHHR group, with P < .05, while the expression of NF-κB p65mRNA decreased significantly in the high-concentration YHHR group, with P < .01. On the other hand, when compared with that in the model group, the expression of NF-κB p65 decreased in the low-concentration YHHR group, but was not statistically significant, while the expression of NF-κB p65 was significant in the high-concentration YHHR group, and has statistical significance with P < .05. YHHR has been shown to resist inflammation and AS through the SRC/NF-κB signaling pathway.

Undescribed amino acid-sesquiterpene lactone adducts and sesquiterpene glycosides from the roots of Saussurea lappa and their anti-HBV activity.

Saussurea lappa (Asteraceae family), a traditional Chinese medicine, has been found to possess anti-inflammatory, immune-promoting, antibacterial, antitumor, anti-HBV, cholestatic, and hepatoprotective activities. Herein, two undescribed amino acid-sesquiterpene lactone adducts, saussureamines G and H (1 and 2), and two new sesquiterpene glycosides, saussunosids F and G (3 and 4), along with 26 known sesquiterpenoids (5-30) have been isolated from the roots of S. lappa. Their structures and absolute configurations of these compounds were established by physical data analyses such as HRESIMS, IR, 1D and 2D NMR and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (5, 6, 12, 13, 17, 19, 23, 26, 29, and 30) exhibited activities against the secretions of HBsAg and HBeAg. In particular, compound 6 showed inhibition of HBsAg and HBeAg secretion with IC50 values of 11.24 and 15.12 µM, with SI values of 1.25 and 0.93, respectively. Molecular docking studies were also conducted on the anti-HBV compounds. Overall, this study provides insights into the potential therapeutic uses of the compounds found in the roots of S. lappa, particularly in the treatment of hepatitis B virus infections.

Artemiprinolides A-M, thirteen undescribed sesquiterpenoid dimers from Artemisia princeps and their antihepatoma activity.

Bioassay-guided investigation of the active fraction of Artemisia princeps led to 13 undescribed sesquiterpenoid dimers, artemiprinolides A-M (1-13), together with 11 known ones (14-24). Their structures were elucidated by comprehensive spectroscopic data and absolute configurations were assigned based on single crystal X-ray diffraction data and ECD calculations. Structurally, all compounds were postulated to be derived from the Diels-Alder cycloaddition. The isolated dimers except 11 and 15 were assayed for their cytotoxicity against HepG2, Huh7, and SK-Hep-1 cell lines, of which four compounds (3, 13, 17, 18) exhibited obvious cytotoxicity with IC50 values ranging from 8.8 to 20.1 µM. Interestingly, the most active compounds 1 and 16 manifested significant cytotoxicity on the three tested hepatoma cell lines with IC50 values of 5.4, 4.1 (HepG2), 7.7, 5.6 (Huh7), and 11.8, 15.7 µM (SK-Hep-1), respectively, which were better than sorafenib. Compound 1 dose-dependently inhibited cell migration and invasion, and significantly induced the HepG2 cell arrest in G2/M phase by downregulating cdc2 and pcdc2 and upregulating cyclinB1; and induced apoptosis by downregulating Bcl-2 expression and upregulating Bax level. The molecular docking study implied that the carbonyl at the C-12' of 1 had a strong binding affinity with PRKACA.

Selenium nanoparticles improve nickel-induced testosterone synthesis disturbance by down-regulating miR-708-5p/p38 MAPK pathway in Leydig cells.

The present study was designed to investigate the role of miR-708-5p/p38 mitogen-activated protein kinase (MAPK) pathway during the mechanism of selenium nanoparticles (Nano-Se) against nickel (Ni)-induced testosterone synthesis disorder in rat Leydig cells. We conducted all procedures based on in vitro culture of rat primary Leydig cells. After treating Leydig cells with Nano-Se and NiSO4 alone or in combination for 24 h, we determined the cell viability, reactive oxygen species (ROS) levels, testosterone production, and the protein expression of key enzymes involved in testosterone biosynthesis: steroidogenic acute regulatory (StAR) and cytochrome P450 cholesterol side chain cleavage enzyme (CYP11A1). The results indicated that Nano-Se antagonized cytotoxicity and eliminated ROS generation induced by NiSO4 , suppressed p38 MAPK protein phosphorylation and reduced miR-708-5p expression. Importantly, we found that Nano-Se upregulated the expression of testosterone synthase and increased testosterone production in Leydig cells. Furthermore, we investigated the effects of p38 MAPK and miR-708-5p using their specific inhibitor during Nano-Se against Ni-induced testosterone synthesis disorder. The results showed that Ni-inhibited testosterone secretion was alleviated by Nano-Se co-treatment with p38 MAPK specific inhibitor SB203580 and miR-708-5p inhibitor, respectively. In conclusion, these findings suggested Nano-Se could inhibit miR-708-5p/p38 MAPK pathway, and up-regulate the key enzymes protein expression for testosterone synthesis, thereby antagonizing Ni-induced disorder of testosterone synthesis in Leydig cells.

Micro-Ultrasound Guided Transperineal Prostate Biopsy: A Clinic-Based Procedure.

Prostate cancer is the most common solid malignancy in men and requires a biopsy for diagnosis. This manuscript describes a freehand micro-ultrasound guided transperineal technique performed under local anesthesia, which maintains accuracy, keeps patients comfortable, has low adverse events, and minimizes the need for disposables. Prior micro-ultrasound-guided transperineal techniques required general or spinal anesthesia. The key steps described in the protocol include (1) the placement of the local anesthesia, (2) micro-ultrasound imaging, (3) and the visualization of the anesthetic/biopsy needle while uncoupled from the insonation plane. A retrospective review of 100 patients undergoing this technique demonstrated a 68% clinically significant cancer detection rate. Pain scores were prospectively collected in a subset of patients (N = 20) and showed a median procedural pain score of 2 out of 10. The 30 day Grade III adverse event rate was 3%; one of these events was probably related to the prostate biopsy. Overall, we present a simple, accurate, and safe technique for performing a micro-ultrasound-guided transperineal prostate biopsy.

[Analysis of acupuncture characteristics in WU's annotation of Biaoyoufu].

Zhenfang Liuji: Kaimeng Ji of DOU's Biaoyoufu (annotated by WU Kun) was written by WU Kun. In WU's annotation of Biaoyoufu, based on the elucidation of DOU's acupuncture thoughts, it embodies WU's acupuncture thoughts, including the importance of the spleen and stomach, treatment by both acupuncture and herbal medicines on the root cause of disease, as well as the mind regulation with acupuncture. Besides, it displays the characteristics of acupuncture techniques and the experience in diagnosis and treatment, e.g. "eight methods of acupuncture prescriptions", "five categories of acupuncture prescriptions", "two chi and two cun" in meridian diagnosis, as well as cataractopiesis with golden needle, reflecting the distinctive and high clinical value.

[Clinical efficacy of shallow-needle therapy combined with estazolam on insomnia of liver stagnation transforming into fire pattern: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of shallow-needle therapy combined with estazolam on insomnia differentiated as liver stagnation transforming into fire and its effect on adrenocorticotropic hormone (ACTH) and cortisol (CORT), so as to explore the mechanism of this combined treatment. METHODS: A total of 119 patients with insomnia of liver stagnation transforming into fire pattern were randomly divided into shallow-needle therapy group (n=40), medication group (n=39), and shallow-needle therapy combined with medication group (combined therapy group,n=40). In the shallow-needle therapy group, the patients were treated with finger pressure and operation with shallow stimulating at Zhenjing (Dong's extra point, sedative point) and Taichong (LR3). In the medication group, the patients were administered with estazolam (1 mg) orally. In the combined therapy group, both shallow-needle therapy and medication were administered. The treatment was given once daily in each group, 10 days as one session of treatment and 2 sessions were required. Before and after the treatment, Pittsburgh sleep quality index scale (PSQI) and Self-rating anxiety scale (SAS) were used to assess sleep and anxiety status. ELISA was used to detect the contents of ACTH and CORT in plasma. The clinical efficacy was evaluated in each group. RESULTS: In within-group comparison, PSQI scores, SAS scores and the concentrations of ACTH and CORT in plasma were all decreased (P<0.05) after treatment for the patients of three groups. After treatment, the total PSQI score, the score for sleep latency, sleep duration and daytime dysfunction, as well as SAS score in the combined therapy group were all lower than those of the shallow-needle therapy group (P<0.05); the total PSQI score, the score for sleep duration and sleep efficiency, as well as SAS score were lower when compared with the medication group (P<0.05). The total effective rates were 87.50% (35/40), 82.05% (32/39) and 95.00% (38/40) in the shallow-needle therapy group, the medication group and the combined therapy group, respectively. The total effective rate in the combined therapy group was higher than those of the shallow-needle therapy group and the medication group separately (P<0.05). CONCLUSION: Shallow-needle therapy combined with estazolam is effective on insomnia of liver stagnation transforming into fire pattern, and its underlying effect mechanism is related to the reduction of plasma ACTH and CORT levels.

Astragaloside IV Protects Sepsis-induced Acute Kidney Injury by Attenuating Mitochondrial Dysfunction and Apoptosis in Renal Tubular Epithelial Cells.

BACKGROUND: Acute kidney injury (AKI) is closely linked to the pathogenesis of sepsis. Oxidative stress can affect the development of AKI by increasing damage to renal tubular epithelial cells. Astragaloside IV (AS-IV) is a natural saponin widly verified beneficial for ameliorating sepsis-induced kidney injury. However, the underlying mechanisms of AS-IV on relieving oxidative stress in renal tubular epithelial cells are yet to be established. PURPOSE: We aimed to investigate whether AS-IV could attenuate mitochondrialdysfunction and apoptosis in renal tubular epithelial cells and reveal its underlying mechanisms. METHODS: For the in vivo study, mice were divided into four groups (n=6): sham+saline, CLP+saline, CLP+ASIV- low dosage (5 mg/kg), CLP+AS-IV-high dosage (10 mg/kg), After 6 h or 24 h of treatment, the renal injuries were assessed based on related parameters of blood, protein and histopathological examination. Immunohistochemistry and ELISA were used to examine renal function. The molecular mechanism of AS-IV inhibited apoptosis and mitochondrial damage were monitored by flow cytometry and western blot analysis in HK-2 cells. RESULTS: We found that AS-IV ameliorates renal vacuolization, brush border loss, mitochondrial ultrastructure changes in sepsis-induced AKI, and the apoptosis and oxidative damage were greatly mitigated by AS-IV (10 mg/kg)-treated group. Abnormal changes in mitochondrial morphology and mitochondrial membrane potential were alleviated, and the expression of mitochondrial complex protein I (NDUFB8) and mitochondrial complex protein II (SDHB8) increased with (10 mg/kg)-treated group. Tubular epithelial cell apoptosis in AS-IV (20 µM)-treated cells was reduced by the Bax and cleaved caspase3 pathway. CONCLUSION: These studies demonstrated that AS-IV protects against sepsis-induced kidney tubular injury by alleviating oxidative stress, mitochondrial dysfunction possibly associated with the restored cleaved caspase3 pathway.

Traditional Chinese medicine: An important source for discovering candidate agents against hepatic fibrosis.

Hepatic fibrosis (HF) refers to the pathophysiological process of connective tissue dysplasia in the liver caused by various pathogenic factors. Nowadays, HF is becoming a severe threat to the health of human being. However, the drugs available for treating HF are limited. Currently, increasing natural agents derived from traditional Chinese medicines (TCMs) have been found to be beneficial for HF. A systemic literature search was conducted from PubMed, GeenMedical, Sci-Hub, CNKI, Google Scholar and Baidu Scholar, with the keywords of "traditional Chinese medicine," "herbal medicine," "natural agents," "liver diseases," and "hepatic fibrosis." So far, more than 76 natural monomers have been isolated and identified from the TCMs with inhibitory effect on HF, including alkaloids, flavones, quinones, terpenoids, saponins, phenylpropanoids, and polysaccharides, etc. The anti-hepatic fibrosis effects of these compounds include hepatoprotection, inhibition of hepatic stellate cells (HSC) activation, regulation of extracellular matrix (ECM) synthesis & secretion, regulation of autophagy, and antioxidant & anti-inflammation, etc. Natural compounds and extracts from TCMs are promising agents for the prevention and treatment of HF, and this review would be of great significance to development of novel drugs for treating HF.

Dietary magnesium intake is protective in patients with periodontitis.

Background: Periodontitis is a chronic inflammatory disease of the oral cavity characterized by inflammation of the periodontal tissue and resorption of the alveolar bone, which has a high incidence and is the main cause of tooth loss in adults. In addition to its role in promoting osteogenesis, magnesium also has a role in regulating the inflammatory response, both systemically and locally. There is growing evidence that magnesium is an important factor in maintaining the normal functioning of the body's immune system. Hypomagnesaemia can lead to a variety of chronic inflammatory diseases throughout the body, including periodontitis. Two-thirds of the US population suffers from magnesium deficiency. The connection between dietary magnesium and periodontitis is unknown. As a result, we set out to investigate the link between dietary magnesium intake and periodontitis. Methods: In this study, we collected data from the National Health and Nutrition Examination Survey (NHANES) database from 2013 to 2014. Through 24-h dietary recalls, information about food consumption was collected. We examined the association between the dietary magnesium and periodontitis using multivariable logistic regression model. Based on odds ratios (OR) and 95% confidence intervals (CIs), a strong association was detected. Results: Multivariable logistic regression analysis showed that the OR for periodontitis comparing the highest to the lowest quintile of dietary magnesium intake was 0.69 (95% CIs = 0.52~0.92). The restricted cubic spline (RCS) analysis showed that the non-linear association between dietary magnesium and periodontitis was statistically significant and that dietary magnesium supplementation reduced the prevalence of periodontitis. Conclusion: Dietary magnesium intake is associated with the prevalence of periodontitis. Dietary magnesium deficiency increases the prevalence of periodontitis.

The T-Type Calcium Channel Cav3.2 in Somatostatin Interneurons in Spinal Dorsal Horn Participates in Mechanosensation and Mechanical Allodynia in Mice.

Somatostatin-positive (SOM+) neurons have been proposed as one of the key populations of excitatory interneurons in the spinal dorsal horn involved in mechanical pain. However, the molecular mechanism for their role in pain modulation remains unknown. Here, we showed that the T-type calcium channel Cav3.2 was highly expressed in spinal SOM+ interneurons. Colocalization of Cacna1h (which codes for Cav3.2) and SOM tdTomato was observed in the in situ hybridization studies. Fluorescence-activated cell sorting of SOM tdTomato cells in spinal dorsal horn also proved a high expression of Cacna1h in SOM+ neurons. Behaviorally, virus-mediated knockdown of Cacna1h in spinal SOM+ neurons reduced the sensitivity to light touch and responsiveness to noxious mechanical stimuli in naïve mice. Furthermore, knockdown of Cacna1h in spinal SOM+ neurons attenuated thermal hyperalgesia and dynamic allodynia in the complete Freund's adjuvant-induced inflammatory pain model, and reduced both dynamic and static allodynia in a neuropathic pain model of spared nerve injury. Mechanistically, a decrease in the percentage of neurons with Aß-eEPSCs and Aß-eAPs in superficial dorsal horn was observed after Cacna1h knockdown in spinal SOM+ neurons. Altogether, our results proved a crucial role of Cav3.2 in spinal SOM+ neurons in mechanosensation under basal conditions and in mechanical allodynia under pathological pain conditions. This work reveals a molecular basis for SOM+ neurons in transmitting mechanical pain and shows a functional role of Cav3.2 in tactile and pain processing at the level of spinal cord in addition to its well-established peripheral role.

Structure-Based Molecular Networking for the Discovery of Anti-HBV Compounds from Saussurea lappa (Decne.) C.B Clarke.

It is a crucial to find target compounds in natural product research. This study presents a concept of structure-guided isolation to find candidate active molecules from herbs. We establish a process of anti-viral sesquiterpene networking. An analysis of the networking suggested that new anti-HBV sesquiterpene may be attributable to eudesmane-, guaiane-, cadinane-, germacane- and bisabolane-type sesquiterpenes. In order to evaluate the efficiency of the structure-based molecular networking, ethanol extract of Saussurea lappa (Decne.) C.B Clarke was investigated, which led to the isolation of two guaiane-type (1 and 14), ten eudesmane-type (2-5 and 8-13), two chain (6 and 7) and one germacrane-type (15) sesquiterpenes, including seven new ones, lappaterpenes A-G (1-7), which are reported on herein. The absolute configurations of the new compounds were established by coupling constants, calculated ECD and ROESY correlations, as well as comparisons of optical rotation values with those of known compounds. The absolute configuration of compound 2 was further confirmed by X-ray diffraction. Compounds 1-15 were evaluated for their potency against hepatitis B virus. Compounds 4, 6, 7 and 9 showed effect on HBsAg with inhibition ratios of more than 40% at 30 µM concentrations. Compounds 14 and 15 inhibited HBsAg secretion with the values of IC50 0.73 ± 0.18 and 1.43 ± 0.54 µM, respectively. Structure-based molecular networking inspired the discovery of target compounds.

Transcutaneous vagus nerve stimulation (tVNS) in stroke: the evidence, challenges and future directions.

Stroke is one of the leading causes of death and disability globally. A significant proportion of stroke survivors are left with long term neurological deficits that have a detrimental effect on personal wellbeing and wider socioeconomic impacts. As such, there is an unmet need for novel therapies that improve neurological recovery after stroke. Invasive vagus nerve stimulation (VNS) paired with rehabilitation has been shown to improve upper limb motor function in chronic stroke. However, invasive VNS requires a surgical procedure and therefore may not be suitable for all stroke patients. Non-invasive, transcutaneous VNS (tVNS) via auricular vagus nerve stimulation in the ear (taVNS) and cervical vagus nerve stimulation in the neck (tcVNS) have been shown to activate similar vagal nerve projections in the central nervous system to invasive VNS. A number of pre-clinical studies indicate that tVNS delivered in acute middle cerebral artery occlusion reduces infarct size through anti-inflammatory effects, reduced excitotoxicity and increased blood-brain barrier integrity. Longer term effects of tVNS in stroke that may mediate neuroplasticity include microglial polarisation, angiogenesis and neurogenesis. Pilot clinical trials of taVNS indicate that taVNS paired with rehabilitation may improve upper limb motor and sensory function in patients with chronic stroke. In this review, we summarise and critically appraise the current pre-clinical and clinical evidence, outline the major ongoing clinical trials and detail the challenges and future directions regarding tVNS in acute and chronic stroke.