[Chemical constituents from roots of Kadsura heteroclita].

The dichloromethane fraction of Kadsura heteroclita roots was separated and purified by chromatographic techniques(e.g., silica gel, Sephadex LH-20, ODS, MCI column chromatography) and semi-preparative HPLC. Twenty compounds were isolated from K. heteroclita, and their structures were identified by NMR, MS, UV, and X-ray single crystal diffraction techniques. Twenty compounds were isolated from K. heteroclita, which were identified as xuetongdilactone G(1), mallomacrostin C(2), 3,4-seco(24Z)-cychmrt-4(28),24-diene-3,26-dioic acid 3-methyl ester(3), nigranoic acid(4), methyl ester schizanlactone E(5), schisandronic acid(6), heteroclic acid(7), wogonin(8),(2R,3R)-4'-O-methyldihydroquercetin(9), 15,16-bisnor-13-oxo-8(17),11E-labdadien-19-oic acid(10), stigmast-4-ene-6ß-ol-3-one(11), psoralen(12),(1R,2R,4R)-trihydroxy-p-menthane(13), homovanillyl alcohol(14), 2-(4-hydroxyphenyl)-ethanol(15), coniferaldehyde(16),(E)-7-(4-hydroxy-3-methoxyphenyl)-7-methylbut-8-en-9-one(17), acetovanillone(18), vanillic acid(19) and vanillin(20). Compound 1 is a new compound named xuetongdilactone G. Compounds 2-3 and 8-20 are isolated from K. heteroclita for the first time.

Melatonin in cancer biology: pathways, derivatives, and the promise of targeted delivery.

Melatonin, historically recognized for its primary role in regulating circadian rhythms, has expanded its influence particularly due to its wide range of biological activities. It has firmly established itself in cancer research. To highlight its versatility, we delved into how melatonin interacts with key signaling pathways, such as the Wnt/ß-Catenin, PI3K, and NF-κB pathways, which play foundational roles in tumor development and progression. Notably, melatonin can intricately modulate these pathways, potentially affecting various cellular functions such as apoptosis, metastasis, and immunity. Additionally, a comprehensive review of current clinical studies provides a dual perspective. These studies confirm melatonin's potential in cancer management but also underscore its inherent limitations, particularly its limited bioavailability, which often relegates it to a supplementary role in treatments. Despite this limitation, there is an ongoing quest for innovative solutions and current advancements include the development of melatonin derivatives and cutting-edge delivery systems. By synthesizing the past, present, and future, this review provides a detailed overview of melatonin's evolving role in oncology, positioning it as a potential cornerstone in future cancer therapeutics.

Coffee Consumption and Incidence of Cardiovascular and Microvascular Diseases in Never-Smoking Adults with Type 2 Diabetes Mellitus.

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

Contribution of activating lateral hypothalamus-lateral habenula circuit to nerve trauma-induced neuropathic pain in mice.

Neuropathic pain, a severe clinical symptom, significantly affects the quality of life in the patients. The molecular mechanisms underlying neuropathic pain have been the focus of research in recent decades; however, the neuronal circuit-mediated mechanisms associated with this disorder remain poorly understood. Here, we report that a projection from the lateral hypothalamus (LH) glutamatergic neurons to the lateral habenula (LHb), an excitatory LH-LHb neuronal circuit, participates in nerve injury-induced nociceptive hypersensitivity. LH glutamatergic neurons are activated and display enhanced responses to normally non-noxious stimuli following chronic constriction injury. Chemogenetic inhibition of LH glutamatergic neurons or excitatory LH-LHb circuit blocked CCI-induced nociceptive hypersensitivity. Activation of the LH-LHb circuit led to augmented responses to mechanical and thermal stimuli in mice without nerve injury. These findings suggest that LH neurons and their triggered LH-LHb circuit participate in central mechanisms underlying neuropathic pain and may be targets for the treatment of this disorder.

Ergostane-type sterols and sesquiterpenes with anti-neuroinflammatory activity from a Nigrograna species associated with Clematis shensiensis.

Nigrograna sp. LY66, an endophytic fungus associated with the herbal medicinal plant Clematis shensiensis, produced four undescribed steroids, nigergostanes A-D (1-4), including an unusual ketal-containing nigergostane (1), and four undescribed sesquiterpenoids decorated with cyclohexanone motifs, nigbisabolanes A-D (7-10), along with three known compounds, 23R-hydroxy-(20Z,24R)-ergosta-4,6,8(14),20(22)-tetraen-3-one (5), ergosta-5,7,22-trien-3ß-ol (6), and curculonone A (11). The structures and absolute configurations of these undescribed compounds were confirmed using spectroscopic data (NMR and HRESIMS), modified Mosher's method, and ECD experiments. Additionally, compounds 5 and 8 displayed significant inhibition of nitric oxide generation in lipopolysaccharide-induced BV-2 microglial cells with IC50 values of 2.8 and 2.7 µM, respectively, and is thus more potent than that of the positive control, quercetin (IC50 = 8.77 µM). A molecular docking study revealed that 23-OH of 5 binds to the Y347 residue of inducible nitric oxide synthase (iNOS), whereas the 2-OH and 9,10-diol moieties of 8 bind to R381 and W463 and haeme residues of iNOS, respectively, which has rarely been reported in previous studies. These findings provide a set of undescribed lead compounds that can be developed into anti-neuroinflammatory agents.

[An anti-scald device for warm needling].

Warm needling, i.e. acupuncture with the needle warmed by burning moxa stick or cone, is frequently employed in the treatment of cold and dampness type disorders. During treatment, accidental skin scald may occur if the burning moxa drops on the skin due to slight changes in patient's body position. Thus, we designed and developed an anti-scald device for warm needling which is suitable for any part of the body. This device is made up of two parts, a stainless steel-grid moxa cartridge (including half cylinder, hinge shaft, lug, limit bar, clamping arm, connecting arm, torsion spring, heat insulation pad, through holes) and a clamp holder which is in an integrated structure. The grid moxa cartridge can be used to wrap the burning mugwort cone in all directions to prevent the ignited moxa-cone from falling and skin scalding, and effectively collect the burned moxa ash. At the same time, the clamp holder can be used to help fix the moxa-cone to increase the stability of warm needling operation. The device is convenient to operate and novel in design, can effectively reduce the occurrence of scald accidents in clinical treatment, save time and manpower, and has both economic and ecological benefits, being helpful to the promotion and use of warm needling.

Programmed pH-responsive core-shell nanoparticles for precisely targeted therapy of ulcerative colitis.

pH-Responsive nanotherapeutics were recently developed for the treatment of ulcerative colitis (UC). However, they target the entire colon rather than the UC site, which leads to insufficient accumulation in inflamed colon lesions and causes side effects. Core-shell nanoparticles exhibit unique advantages in improving the precision of targeted delivery. In this study, Eudragit® EPO and L100, two pH-sensitive materials, were coated on nano-sized curcumin to fabricate core-shell nanoparticles. The developed CNs@EPO@L100 exhibited programmed pH-responsive drug release behavior, improved in vitro anti-inflammatory ability, and enhanced accumulation at the site of inflammation in the colon. Furthermore, after oral administration, CNs@EPO@L100 significantly ameliorated the inflammatory symptoms in mice. Taken together, this study provides insights into programmed release through the rational application of pH-sensitive materials and offers strategies for a precisely targeted therapy of UC using core-shell nanoparticles.

[Effect of electroacupuncture on the expressions of TRPV1, P2X3 receptors in bladder of rats with interstitial cystitis].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL 32) and "Huiyang" (BL 35) on the pain, urodynamic and the expressions of transient receptor poteintial vanilloid 1 (TRPV1) and P2X3 receptors in bladder of rats with interstitial bladder (IC), and to explore the possible mechanism on EA for IC. METHODS: A total of 24 Wistar female rats were randomly divided into a blank group, a model group and an EA group, 8 rats in each group. In the model group and the EA group, IC model was established by intraperitoneal injection of cyclophosphamide by 150 mg/kg at once. EA was applied at "Ciliao" (BL 32) and "Huiyang" (BL 35) in the EA group for 20 min, with continuous wave, 30 Hz in frequency, once a day for 3 consecutive days. Mechanical pain threshold of bladder and urodynamic indexes (first urination time, bladder effective volume and urination pressure) were observed after model establishment and after intervention, the expressions of TRPV1 and P2X3 receptors in the bladder were detected by Western blot. RESULTS: After model establishment, the mechanical pain threshold of bladder was decreased in the model group and the EA group compared with that in the blank group (P<0.01). After intervention, the mechanical pain threshold of bladder in the model group was lower than the blank group (P<0.01), and that in the EA group was higher than the model group (P<0.01). The urodynamic of the rats in the blank group was normal, obvious abnormal contraction during the filling period of bladder was found in the rats of the model group, while no abnormal contraction during the filling period was found in the rats of the EA group. After model establishment, in the model group and the EA group, the first urination time was earlier than the blank group (P<0.01), while bladder effective volume and urination pressure were lower than the blank group (P<0.01). After intervention, in the model group, the first urination time was earlier than the blank group (P<0.01), while bladder effective volume and urination pressure were lower than the blank group (P<0.05); in the EA group, the first urination time was later than the model group (P<0.05), while bladder effective volume and urination pressure were higher than the model group (P<0.05). Compared with the blank group, the protein expressions of TRPV1 and P2X3 receptors in bladder were up-regulated in the model group (P<0.01); compared with the model group, the protein expressions of TRPV1 and P2X3 receptors in bladder were down-regulated in the EA group (P<0.05). CONCLUSION: EA can relieve bladder pain and improve urodynamic in IC rats. The mechanism may be related to the down-regulation on the expressions of TRPV1 and P2X3 receptors and the further inhibition on the abnormal input of bladder signal.

Touch-sensitive stamens enhance pollen dispersal by scaring away visitors.

Animal-pollinated plants have to get pollen to a conspecific stigma while protecting it from getting eaten. Touch-sensitive stamens, which are found in hundreds of flowering plants, are thought to function in enhancing pollen export and reducing its loss, but experimental tests are scarce. Stamens of Berberis and Mahonia are inserted between paired nectar glands and when touched by an insect's tongue rapidly snap forward so that their valvate anthers press pollen on the insect's tongue or face. We immobilized the stamens in otherwise unmodified flowers and studied pollen transfer in the field and under enclosed conditions. On flowers with immobilized stamens, the most common bee visitor stayed up to 3.6× longer, yet removed 1.3× fewer pollen grains and deposited 2.1× fewer grains on stigmas per visit. Self-pollen from a single stamen hitting the stigma amounted to 6% of the grains received from single bee visits. Bees discarded pollen passively placed on their bodies, likely because of its berberine content; nectar has no berberine. Syrphid flies fed on both nectar and pollen, taking more when stamens were immobilized. Pollen-tracking experiments in two Berberis species showed that mobile-stamen-flowers donate pollen to many more recipients. These results demonstrate another mechanism by which plants simultaneously meter out their pollen and reduce pollen theft.

[Research progress on pharmacology of butylphthalide and its derivatives].

The butylphthalide(NBP), a colorless or light yellow viscous oily component isolated from celery seeds, has the effects of anti-inflammation, anti-oxidative stress, protecting blood-brain barrier, improving cerebral microcirculation, and promoting angiogenesis. It can protect the neurological function of patients with ischemic stroke through a variety of mechanisms, improve the symptoms of patients, and contribute to the long-term recovery of them. Therefore, independently developed in China, NBP was approved by State Food and Drug Administration for the clinical treatment of stroke patients in 2002. At the same time, owing to the complex multi-target pharmacological mechanism, NBP has been frequently used in clinical practice. As frequently verified, it has obvious effects in the treatment of other neurological diseases such as Alzheimer's disease, vascular dementia, Parkinson's disease, autoimmune diseases, depression, traumatic central nervous system injury. Moreover, it demonstrates significant pharmacological effects on non-neurological diseases such as diabetes mellitus and myocardial infarction. Therefore, this study summarizes the research progress on roles of NBP in nervous system diseases and non-nervous system diseases, and the pharmacological characteristics and mechanisms of NBP, which is expected to lay a basis for research on related targets.

Whey protein supplementation improves postprandial glycemia in persons with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

Whey protein (WP) can increase insulin secretion, produce an incretin effect, delay gastric emptying, and regulate appetite, resulting in improved glycemic control. We hypothesized that WP supplementation is associated with postprandial glycemia regulation in persons with type 2 diabetes mellitus (T2DM) and conducted a quantitative meta-analysis of randomized controlled trials (RCTs) to test this hypothesis. We searched PubMed, Embase, Cochrane Library, Scopus databases, and the ClinicalTrials.gov registry for relevant RCTs published before March 2022. We assessed the pooled effects using a random-effects model on glucose and insulin levels at 60 and 120 minutes, total glucagon-like peptide-1 (tGLP-1) at 30 and 60 minutes, and the incremental area under the curve (iAUC) of glucose, insulin, tGLP-1, and glucose-dependent insulinotropic polypeptide. Five RCTs involving 134 persons were included. Postprandial glycemia was significantly lower at 60 minutes (weighted mean difference: -2.67 mmol/L; 95% confidence interval, -3.62 to -1.72 mmol/L) and 120 minutes (-1.59 mmol/L; -2.91 to -0.28 mmol/L) in WP group than in placebo group. The iAUC of insulin was significantly higher in WP group (24.66 nmol/L × min, 1.65-47.66 nmol/L × min) than in placebo group. Although other results favored the WP group, differences between the groups were not statistically significant. The present study showed that premeal WP supplementation is beneficial for postprandial glycemia in persons with mild or well-controlled T2DM without substantial adverse effects. However, the level of certainty of current evidence is not high enough. Further larger and well-designed clinical trials are warranted for evaluating optimal dose and long-term effects of WP supplementation.

New Advances of CRISPR/Cas9 Technique and its Application in Disease Treatment and Medicinal Plants Research.

BACKGROUND: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology is widely used in disease treatment and medicinal plant improvements due to its advantages, such as easy operation, low time consumption, and high efficiency. However, potential off-target risks still exist in practical applications and need to be solved urgently. OBJECTIVES: This study aimed to review the application progress of CRISPR/Cas9 technology in the field of disease treatment and medicinal agriculture in recent years. Furthermore, the study discusses the ways to reduce the off-target effect of CRISPR/Cas9 technology, providing a reference for the further application of this technology. METHODS: CiteSpace software was used to analyze relevant literature data from 2013 to August 2021, and search results were retrieved from Web of Science, PubMed, and CNKI databases. RESULTS: In the field of disease treatment, CRISPR/Cas9 technology has great potential to cure challenging human diseases and has been widely used in drug target development, drug design, and screening. In crop breeding, CRISPR/Cas9 accelerates the improvement of crop varieties and shortens the number of years of crop breeding. By adjusting the length and GC content of sgRNA and changing the concentration of Cas9/sgRNA complex to reduce the off-target effect of CRISPR/Cas9 technology, the target genes can be manipulated more accurately. CONCLUSION: CRISPR/Cas9 technology is an indispensable and key technology in the field of disease treatment and medicinal plants. With the in-depth study of the off-target effect, CRISPR/Cas9 technology can have broader application prospects in the fields of medicine and medicinal agriculture.

Slow development allows redundant genes to restore the fertility of rpg1, a TGMS line in Arabidopsis.

Slow development has been shown to be a general mechanism to restore the fertility of thermo-sensitive and photoperiod-sensitive genic male sterile (TGMS and PGMS) lines in Arabidopsis. rpg1 is a TGMS line defective in primexine, which is essential for pollen wall pattern formation. Here, we showed that RPG1-GFP was highly expressed in microsporocytes, microspores, and pollen grains but not in the tapetum in the complemented transgenic line, suggesting that microsporocytes are the main sporophytic cells for primexine formation. Further cytological observations showed that primexine formation in rpg1 was partially restored under slow growth conditions, leading to its fertility restoration. RPG2 is the homolog of RPG1 in Arabidopsis. We revealed that the fertility recovery of rpg1 rpg2 was significantly reduced compared with that of rpg1 under low temperature. The RPG2-GFP protein was also expressed in microsporocytes in the RPG2-GFP (WT) transgenic line. These results suggest that RPG2 plays a redundant role in rpg1 fertility restoration. rpg1 plants were male sterile at the early growth stage, while their fertility was partially restored at the late developmental stage. The fertility of the rpg1 lateral branches was also partially restored. Further growth analysis showed that slow growth at the late reproductive stage or on the lateral branches led to fertility restoration. This work reveals the importance of gene redundancy in fertility restoration for TGMS lines and provides further insight into pollen wall pattern formation.

[Effect of Gegen Qinlian Decoction on gut microbiota of irritable bowel syndrome with diarrhea rats].

This study aims to explore the effect of Gegen Qinlian Decoction on gut microbiota of irritable bowel syndrome with diarrhea(IBS-D) rats. A total of 36 male SD rats were randomly classified into the control group, model group, rifaximin group(150 mg·kg~(-1)), and high-dose(8.125 g·kg~(-1)), medium-dose(4.062 5 g·kg~(-1)) and low-dose(2.031 3 g·kg~(-1)) Gegen Qinlian Decoction groups with the random number table method, 6 in each group. After modeling, rats were treated for 8 days. The general state, bristol stool chart(BSC) score, and the minimum volume threshold for abdominal withdrawal reflex were recorded. Pathological changes of colon tissues were observed based on hematoxylin and eosin(HE) staining, and gut microbiota was analyzed based on 16 S rRNA sequencing. Compared with the model group, rifaximin group and high-dose and medium-dose Gegen Qinlian Decoction groups showed low BSC score(P<0.01) and high minimum volume threshold for abdominal lifting(P<0.05). HE staining showed that Gegen Qinlian Decoction could relieve intestinal inflammation. 16 S rRNA sequencing suggested obvious variation of gut microbiota in IBS-D rats. Gegen Qinlian Decoction significantly raised the richness index and diversity index of gut microbiota, regulated the number of the flora, and improved alpha diversity and beta diversity. Species composition of gut microbiota and LEfSe analysis showed that Gegen Qinlian Decoction could significantly increase the ratio of Bacteroidota to Firmicutes, elevate the abundance of probiotics such as Clostridia and Lachnospirales, and reduce the abundance of conditional pathogens such as Bacteroidales, and Prevotellaceae. PICRUSt2 analysis indicated that Gegen Qinlian Decoction was mainly related to multiple metabolic pathways such as carbohydrate metabolism and amino acid metabolism. In summary, Gegen Qinlian Decoction can significantly reduce visceral hypersensitivity of IBS-D rats, alleviate intestinal inflammation, and relieve clinical symptoms such as diarrhea. The mechanism is the likelihood that it regulates the composition and structure of gut microbiota and improves its metabolic pathway as well.

[Cloning and prokaryotic expression of 3-ketoacyl-CoA thiolase gene AIKAT from Atractylodes lancea].

In this study, the gene encoding the key enzyme 3-ketoacyl-CoA thiolase(KAT) in the fatty acid ß-oxidation pathway of Atractylodes lancea was cloned. Meanwhile, bioinformatics analysis, prokaryotic expression and gene expression analysis were carried out, which laid a foundation for the study of fatty acid ß-oxidation mechanism of A. lancea. The full-length sequence of the gene was cloned by RT-PCR with the specific primers designed according to the sequence information of KAT gene in the transcriptomic data of A. lancea and designated as AIKAT(GenBank accession number MW665111). The results showed that the open reading frame(ORF) of AIKAT was 1 323 bp, encoding 440 amino acid. The deduced protein had a theoretical molecular weight of 46 344.36 and an isoelectric point of 8.92. AIKAT was predicted to be a stable alkaline protein without transmembrane segment. The secondary structure of AIKAT was predicted to be mainly composed of α-helix. The tertiary structure of AIKAT protein was predicted by homology modeling method. Homologous alignment revealed that AIKAT shared high sequence identity with the KAT proteins(AaKAT2, CcKAT2, RgKAT and AtKAT, respectively) of Artemisia annua, Cynara cardunculus var. scolymus, Rehmannia glutinosa and Arabidopsis thaliana. The phylogenetic analysis showed that AIKAT clustered with CcKAT2, confirming the homology of 3-ketoacyl-CoA thiolase genes in Compositae. The prokaryotic expression vector pET-32 a-AIKAT was constructed and transformed into Escherichia coli BL21(DE3) for protein expression. The target protein was successfully expressed as a soluble protein of about 64 kDa. A real-time quantitative PCR analysis was performed to profile the AIKAT expression in different tissues of A. lancea. The results demonstrated that the expression level of AIKAT was the highest in rhizome, followed by that in leaves and stems. In this study, the full-length cDNA of AIKAT was cloned and expressed in E. coli BL21(DE3), and qRT-PCR showed the differential expression of this gene in different tissues, which laid a foundation for further research on the molecular mechanism of fatty acid ß-oxidation in A. lancea.

Influence of diverse natural biopolymers on the physicochemical characteristics of borage seed oil-peppermint oil loaded W/O/W nanoemulsions entrapped with lycopene.

Borage seed oil (BSO), peppermint oil (PO) and lycopene (LC) have accomplished a lot of interest due to their therapeutic benefits in the food and pharmaceutical sectors. However, their employment in functional food products and dietary supplements is still precluded by their high susceptibility to oxidation. Thus, the encapsulation can be applied as a promising strategy to overcome these limits. In the present study, doubly layered water/oil/water (W/O/W) nanoemulsions were equipped using purity gum ultra (PGU), soy protein isolate (SPI), pectin (PC), whey protein isolate (WPI) and WPI-PC and SPI-PC complexes, and their physico-chemical properties were investigated. Our aim was to investigate the influence of natural biopolymers as stabilizers on the physicochemical properties of nanoemulsified BSO, PO and lycopene thru W/O/W emulsions. The droplet size of the fabricated emulsions coated with PGU, WPI, SPI, PC, WPI-PC, and SPI-PC was 156.2, 265.9, 254.7, 168.5, 559.5 and 656.1 nm, correspondingly. The encapsulation efficiency of the entrapped bioactives for powders embedded by PGU, WPI, SPI, PC, WPI-PC, and SPI-PC was 95.21%, 94.67%, 97.24%, 92.19%, 90.07% and 92.34%, respectively. In addition, peroxide and p-anisidine values were used to measure the antioxidant potential of the entrapped bioactive compounds during storage, which was compared to synthetic antioxidant and bare natural antioxidant. The collected findings revealed that oxidation occurred in oils encompassing entrapped bioactive compounds, but at a lower extent than for non-encapsulated bioactives. In summary, the findings obtained from current research prove that the nanoencapsulation of BSO surrounded by innermost aqueous stage of W/O/W improved its stability as well as allowed a controlled release of the entrapped bioactives. Thus, the obtained BSO-PO-based systems could be successfully used for further fortification of food-stuffs.

Conservation Genomics of Wild Red Sage (Salvia miltiorrhiza) and Its Endangered Relatives in China: Population Structure and Interspecific Relationships Revealed From 2b-RAD Data.

Red sage (Salvia miltiorrhiza) is a widely used medicinal plant for treatment of cardiovascular and cerebrovascular diseases. Because of excessive excavation by huge market demand and habitat loss by human activities, the wild population resources of S. miltiorrhiza have reduced drastically in recent years. Meanwhile, population status of two closely related species S. bowleyana and S. paramiltiorrhiza were in a trend of decreasing due to their potential replacement of S. miltiorrhiza. Particularly, S. paramiltiorrhiza was threatened and endemic to a small region in eastern China. However, to date there has been no conservation genetic research reported for wild S. miltiorrhiza population and its endangered relatives. Assess the wild germplasm diversity for S. miltiorrhiza and its related species would provide fundamental genetic background for cultivation and molecular breeding of this medicinally important species. In the present study, we investigated the genetic diversity, population structure, and intra/inter-specific differentiation of S. miltiorrhiza and above two relatives using 2b-RAD genome-wide genotyping method. By investigating 81 individuals of S. miltiorrhiza, 55 individuals of S. bowleyana and 15 individuals of S. paramiltiorrhiza from 23 locations in China, we obtained 23,928 SNPs in total. A comparatively high genetic diversity was observed in S. miltiorrhiza (π = 0.0788, H e = 0.0783 ± 0.0007). The observed and expected heterozygosity in populations of these three species ranged from 0.0297 to 0.1481 and 0.0251 to 0.831, respectively. Two major lineage groups were detected in the examined S. miltiorrhiza populations. The results indicated that Dabie Mountain as a genetic diversity center of S. miltiorrhiza and possible complex inter-specific genetic exchange/hybridization occurred between S. miltiorrhiza and the two relatives. We suggest that strategic conservation and germplasm preservation should be considered not only for wild populations of S. miltiorrhiza, but also for its related S. bowleyana and S. paramiltiorrhiza.

Rational design of a prodrug to inhibit self-inflammation for cancer treatment.

Photothermal therapy (PTT) has been extensively used as an effective therapeutic approach against cancer. However, PTT can trigger the proinflammatory response of dendritic cells (DCs) and macrophages to release proinflammatory cytokines, which can simulate tumor regeneration and further hinder subsequent therapy. Hence, an effective therapeutic system, comprising gold nanoparticle modified Cu2ZnSnS4 nanocrystals and aspirin (Au-CZTS/Asp), was developed to co-deliver PTT agents and inflammatory inhibitors for the synergistic treatment of cancer. Au-CZTS with high near infrared (NIR) photothermal conversion abilities can effectively induce apoptosis and tumor ablation under NIR light. Furthermore, Asp can inhibit the activation of the cGAS-STING pathway in DCs and the polarization of macrophages to intercept the PTT mediated inflammatory responses. Therefore, the as-prepared Au-CZTS/Asp can effectively realize the integration of tumor treatment and recovery. Simultaneously, the Au-CZTS/Asp with ultrasmall size can be rapidly cleared to reduce biotoxicity and side effects. In addition, the Au-CZTS/Asp showed excellent photoacoustic (PA) imaging properties around the tumor in vivo. Thus, our study provides a potential platform for a nano-prodrug that is viable for cancer diagnostic-treatment-recovery integration.

Volatile Oil of Platycladus Orientalis (L.) Franco Leaves Exerts Strong Anti-inflammatory Effects via Inhibiting the IκB/NF-κB Pathway.

This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1ß and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.

Recent Progress in Saikosaponin Biosynthesis in Bupleurum.

BACKGROUND: Chaihu is a popular traditional Chinese medicine that has been used for centuries. It is traditionally used to treat cold fever and liver-related diseases. Saikosaponins (SSs) are one of the main active components of chaihu, in addition to essential oils, flavonoids, and polysaccharides. Considerable effort is needed to reveal the biosynthesis and regulation of SSs on the basis of current progress. OBJECTIVE: The aim of this study is to provide a reference for further studies and arouse attention by summarizing the recent achievements of SS biosynthesis. METHODS: All the data compiled and presented here were obtained from various online resources, such as PubMed Scopus and Baidu Scholar in Chinese, up to October 2019. RESULTS: A few genes of the enzymes of SSs participating in the biosynthesis of SSs were isolated. Among these genes, only the P450 gene was verified to catalyze the SS skeleton ß-amyrin synthase. Several UDP-glycosyltransferase genes were predicted to be involved in the biosynthesis of SSs. SSs could be largely biosynthesized in the phloem and then transported from the protoplasm, which is the biosynthetic site, to the vacuoles to avoid self-poisoning. As for the other secondary metabolites, the biosynthesis of SSs was strongly affected by environmental factors and the different species belonging to the genus of Bupleurum. Transcriptional regulation was studied at the molecular level. CONCLUSION: Profound discoveries in SSs may elucidate the mechanism of diverse the monomer formation of SSs and provide a reference for maintaining the stability of SS content in Radix Bupleuri.