The effect of micronutrient on thyroid cancer risk: a Mendelian randomization study.

Background: The effect of micronutrients on thyroid cancer has been studied in observational studies, however, the cause of relationships has not yet been determined. Thyroid cancer was the subject of a Mendelian randomization (MR) analysis of micronutrients. Aimed to determine whether micronutrient intake has a causal impact on the chance of developing thyroid cancer. Methods: We used a Mendelian randomization (MR) analysis with two samples. Our circulation levels of Cu, Ir, Zn, Ca, VD, and VC were reflected by genetic variations reported from GWAS in individuals of European ancestry. For the GWAS outcome of thyroid cancer. Sensitivity studies that included MR-Egger, weighted median/mode tests, and a more open selection of variations at a genome-wide sub-significant threshold were added to our inverse-variance weighted (IVW) MR study. Results: Using the IVW approach, we did not find evidence that any of the micronutrients to thyroid cancer (Cu: odds ratio [OR = 0.88, p = 0.41]; Zn: odds ratio [OR = 0.87, p = 0.40]; Ir: odds ratio [OR = 1.18, p = 0.39]; Ca: odds ratio [OR = 1.12, p = 0.43]; VC: odds ratio [OR = 0.95, p = 0.22]; VD: odds ratio [OR = 0.89, p = 0.04]). The heterogeneity (p > 0.05) and pleiotropy (p > 0.05) testing provided confirmatory evidence for the validity of our MR estimates. Conclusion: This study does not provide evidence that supplementation with micronutrients including Cu, Ir, Zn, Ca, VD, and VC can prevent thyroid cancer.

Tangshen formula protects against podocyte apoptosis via enhancing the TFEB-mediated autophagy-lysosome pathway in diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease and currently there are no specific and effective drugs for its treatment. Podocyte injury is a detrimental feature and the major cause of albuminuria in DN. We previously reported Tangshen Formula (TSF), a Chinese herbal medicine, has shown therapeutic effects on DN. However, the underlying mechanisms remain obscure. AIM OF THE STUDY: This study aimed to explore the protective effect of TSF on podocyte apoptosis in DN and elucidate the potential mechanism. MATERIALS AND METHODS: The effects of TSF were assessed in a murine model using male KKAy diabetic mice, as well as in advanced glycation end products-stimulated primary mice podocytes. Transcription factor EB (TFEB) knockdown primary podocytes were employed for mechanistic studies. In vivo and in vitro studies were performed and results assessed using transmission electron microscopy, immunofluorescence staining, and western blotting. RESULTS: TSF treatment alleviated podocyte apoptosis and structural impairment, decreased albuminuria, and mitigated renal dysfunction in KKAy mice. Notably, TSF extracted twice showed a more significant reduction in proteinuria than TSF extracted three times. Accumulation of autophagic biomarkers p62 and LC3, and aberrant autophagic flux in podocytes of DN mice were significantly altered by TSF therapy. Consistent with the in vivo results, TSF prevented the apoptosis of primary podocytes exposed to AGEs and activated autophagy. However, the anti-apoptosis capacity of TSF was countered by the autophagy-lysosome inhibitor chloroquine. We found that TSF increased the nuclear translocation of TFEB in diabetic podocytes, and thus upregulated transcription of its several autophagic target genes. Pharmacological activation of TFEB by TSF accelerated the conversion of autophagosome to autolysosome and lysosomal biogenesis, further augmented autophagic flux. Conversely, TFEB knockdown negated the favorable effects of TSF on autophagy in AGEs-stimulated primary podocytes. CONCLUSIONS: These findings indicate TSF appears to attenuate podocyte apoptosis and promote autophagy in DN via the TFEB-mediated autophagy-lysosome system. Thus, TSF may be a therapeutic candidate for DN.

Improvement of sea buckthorn (Hippophae rhamnoides L.) flavonoids on the antioxidant and immune performance of Yellow River carp (Cyprinus carpio L.) fed high-carbohydrate diet.

High-carbohydrate (HC) diets may lead to the deterioration of the antioxidant and immune properties of Yellow River carp and the healthy development of the industry. Studies in mammals have found that sea buckthorn flavonoids (SF) improve antioxidant and immune performance. Therefore, this study comprehensively evaluated the effects of SF on Yellow River carp using in vitro and feeding trials with an HC diet. Control (C, 27.23 %), high-carbohydrate (HC, 42.99 %), and HC + SF (0.1 %, 0.2 %, and 0.4 %) groups were studied in a 10-week aquaculture experiment. The main findings were as follows: (1) SF scavenged O2·-, ·OH, and DPPH free radicals in vitro, which gradually increased with the SF concentration. (2) The antioxidant and immune performance of Yellow River carp was enhanced by dietary supplementation with SF, which involved the regulation of activities of antioxidant and immune enzymes, as well as their changes at the transcription and protein levels. In terms of antioxidant properties, compared to the HC group, HC + SF significantly decreased the activities of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase and the contents of H2O2 and malondialdehyde in the serum and hepatopancreas. The activities of glutathione, glutathione-Px, superoxide dismutase, catalase, and total antioxidant activity in the HC-diet group. In contrast, the addition of SF increased antioxidant enzyme activity. In the hepatopancreas and muscles, SF regulated and activated Nrf2-Keap1, a key signaling pathway for oxidative stress. SF significantly increased the mRNA expression levels of downstream genes (gr, ho-1, cat, and sod) regulated by nrf2. In terms of immune performance, 0.4 % SF markedly increased the activity of immune-related enzymes. SF inhibited the gene expression of pro-inflammatory factors induced by the HC diet and promoted the gene expression of anti-inflammatory factors. In addition, the resistance of Yellow River carp to Aeromonas hydrophila was enhanced by SF. In summary, SF supplementation can reduce oxidative stress and inflammatory harm caused by the HC diet and improve the antioxidant and immune performance of Yellow River carp to varying degrees.

Research progress in the quality evaluation of Salvia miltiorrhiza based on the association of 'morphological features - functional substances - pharmacological action - clinical efficacy'.

Background: Salvia miltiorrhiza (Salvia miltiorrhiza Radix et Rhizoma) is the dried root and rhizome of Salvia miltiorrhiza Bge., a plant of the labiate family. It is a type of traditional Chinese medicine that can promote blood circulation for removing blood stasis. It is often used to treat cardiovascular and cerebrovascular diseases in a clinic.Aim of the study: High-quality Chinese herbal medicines are the premise of the safe and effective use of Traditional Chinese Medicine (TCM) in clinics. We aim to prove the rationality of the traditional identification method, namely, 'the redder the root colour and the thicker the root, the better is the quality', to use the morphological features of Salvia miltiorrhiza as the main index to quickly and directly evaluate its quality. Materials and methods: By referring to relevant ancient books, domestic and foreign literature, and academic papers, we summarised the research progress regarding the morphological features, functional substances, pharmacological action, and clinical efficacy of Salvia miltiorrhiza. Results: The redder the colour, the thicker the root, and the denser the texture, the better is the quality of Salvia miltiorrhiza. In Salvia miltiorrhiza, tanshinone ⅡA and salvianolic acid B are the main functional substances that protect the cardiovascular and cerebrovascular functions. The higher the content of these two functional substances, the better is the clinical efficacy of Salvia miltiorrhiza. Conclusion: The research idea of the correlation between the 'morphological features, functional substances, pharmacological action, and clinical efficacy' can be applied to evaluate the quality of Salvia miltiorrhiza. This research idea and method can also be applied to more Chinese herbal medicines.

Quantification of Caffeoylquinic Acids and Triterpenes as Targeted Bioactive Compounds of Centella asiatica in Extracts and Formulations by Liquid Chromatography Mass Spectrometry.

Centella asiatica (CA) is a culinary vegetable and well-known functional food that is widely used as a medicinal herb and dietary supplement. CA is rich in pentacyclic triterpenes (TTs), including asiaticoside (AS), madecassoside (MS) and the related aglycones asiatic acid (AA), madecassic acid (MA). Traditionally, TTs have been associated with the bioactivity and health promoting effect of CA. Recently, mono-caffeoylquinic acids (MonoCQAs) and di-caffeoylquinic acids (DiCQAs) have been found to contribute to the bioactivity of CA as well. This work reports an analytical strategy based on liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM-MS) for the simultaneous rapid and accurate quantification of 12 bioactive compounds in CA, namely AS, MS, AA, MA, 5-CQA, 4-CQA, 3-CQA, 1,3-DiCQA, 3,4-DiCQA, 1,5-DiCQA, 3,5-DiCQA, 4,5-DiCQA. Method selectivity, accuracy, precision, repeatability, robustness, linearity range, limit of detection (LOD), and limit of quantitation (LOQ) were validated. The validated LC-MRM-MS method has been successfully applied to quantify the 12 bioactive compounds in CA aqueous extracts and two related formulations: a standardized CA product (CAP) used in a phase I clinical trial and formulated CA rodent diets used in preclinical studies. The validated method allows us to support the standardization of CA products used for clinical trials and conduct routine LC-MRM-MS analyses of formulated preclinical diets to confirm correct levels of CA phytochemical markers.

The effects of protein-rich extract from Rhizoma Gastrodiae against cerebral ischemia/reperfusion injury via regulating MAPK and PI3K/AKT signaling pathway.

BACKGROUND: Rhizoma Gastrodiae is a highly valuable traditional Chinese medicine and functional health food that has been used in China to treat neurological disorders for thousands of years. Rhizoma Gastrodiae contains various of biological activities, such as antioxidative, neuroprotective, learning improvement, anxiolytic, and antidepressant effects. However, no studies have been conducted to explore the effects of the protein components in Rhizoma Gastrodiae (GEPS) and its potential protective effects against ischemic stroke.Our main goal was to investigate the effects of GEPS on ischemia/reperfusion (I/R) injury and its possible mechanisms. METHODS: A middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia mouse model and an oxygen-glucose deprivation (OGD/R) injury model in HT22 cells were established. A neurobehavioral test was performed 24 h after MCAO, and brain infarction was measured. A Morris water maze experiment was conducted on Day 14 after reperfusion in mice. Hematoxylin and eosin (HE) and TUNEL staining were performed to assess apoptotic neuronal death. Immunohistochemical analysis was used to detect BDNF and GAP43 expression. The content of SOD, MDA, GSH-PX and ROS were detected. The protein expression was analyzed using Western blotting. Cell viability was determined by MTT assay. Cell apoptosis was examined by flow cytometry. RESULTS: GEPS reduced apoptosis, decreased cerebral infarction, improved neurological defects, and ameliorated oxidative stress in the ischemic penumbra. In addition, GEPS increased the expression of BDNF and GA43 in the penumbra. Mechanistically, GEPS counteracted MCAO-induced PI3K/AKT inhibition and activation of MAPK signaling pathways. CONCLUSION: GEPS has a clear neuroprotective effect on I/R injury, and its mechanism may be linked to the PI3K/AKT and MAPK signaling pathways.

Auricular acupuncture for persistent insomnia and anxiety associated with COVID-19: a case report.

The coronavirus disease 2019 (COVID-19) has been associated with various psychological symptoms. We report a case of a female patient who was diagnosed with persistent insomnia and anxiety associated with COVID-19, which was successfully treated with nine treatment sessions of auricular acupuncture. This case report provides preliminary evidence to support further research into auricular acupuncture as a potential therapy for persistent insomnia and anxiety associated with COVID-19.

Therapeutic application of traditional Chinese medicine in kidney disease: Sirtuins as potential targets.

Sirtuins are a family of NAD+ III-dependent histone deacetylases that consists of seven family members, Sirt1-Sirt7, which regulate various signalling pathways and are involved in many critical biological processes of kidney diseases. Traditional Chinese medicine (TCM), as an essential part of the global healthcare system, has multi-component and multi-pathway therapeutic characteristics and plays a role in preventing and controlling various diseases. Through ongoing collaboration with modern medicine, TCM has recently achieved many remarkable advancements in theoretical investigation, mechanistic research, and clinical applications related to kidney diseases. Therefore, a comprehensive and systematic summary of TCM that focuses on sirtuins as the intervention target for kidney diseases is necessary. This review introduces the relationship between abnormal sirtuins levels and common kidney diseases, such as diabetic kidney disease and acute kidney injury. Based on the standard biological processes, such as inflammation, oxidative stress, autophagy, mitochondrial homeostasis, and fibrosis, which are underlying kidney diseases, comprehensively describes the roles and regulatory effects of TCM targeting the sirtuins family in various kidney diseases.

Chlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Centella asiatica Extracts That Mediate Resilience to Chronic Stress in Drosophila melanogaster.

Common symptoms of depressive disorders include anhedonia, sleep problems, and reduced physical activity. Drugs used to treat depression mostly aim to increase serotonin signaling but these can have unwanted side effects. Depression has also been treated by traditional medicine using plants like Centella asiatica (CA) and this has been found to be well tolerated. However, very few controlled studies have addressed CA's protective role in depression, nor have the active compounds or mechanisms that mediate this function been identified. To address this issue, we used Drosophila melanogaster to investigate whether CA can improve depression-associated symptoms like anhedonia and decreased climbing activity. We found that a water extract of CA provides resilience to stress induced phenotypes and that this effect is primarily due to mono-caffeoylquinic acids found in CA. Furthermore, we describe that the protective function of CA is due to a synergy between chlorogenic acid and one of its isomers also present in CA. However, increasing the concentration of chlorogenic acid can overcome the requirement for the second isomer. Lastly, we found that chlorogenic acid acts via calcineurin, a multifunctional phosphatase that can regulate synaptic transmission and plasticity and is also involved in neuronal maintenance.

Wrist-ankle acupuncture combined with pain nursing for the treatment of urinary calculi with acute pain.

BACKGROUND: Urological calculi often cause renal colic, which is characterized by paroxysmal or persistent severe pain in the upper abdomen or lumbar region. Development of methods to quickly relieve these pain symptoms has garnered clinical attention. Wrist-ankle acupuncture is a type of floating acupuncture therapy administered at selected points in the carpal and ankle areas, and it has good pain-relieving effects. We used wrist-ankle acupuncture combined with pain nursing for pain intervention in patients with renal calculi to confirm its application and safety. AIM: To study the effect of wrist-ankle acupuncture combined with pain nursing in the treatment of urinary calculi with acute pain. METHODS: Eighty-two patients with urinary calculi with acute pain as the first symptom followed at our hospital from November 2019 to June 2021 were enrolled in the study and classified into two groups according to the odd and even numbers of the visit sequences, each with 41 cases. The control group received a routine nursing intervention and intramuscular injection of nonsteroidal anti-inflammatory drugs, whereas the observation group received pain management nursing and wrist-ankle acupuncture. Subsequently, the pain-relieving effect was compared between the two groups. RESULTS: The score on the visual analog scale (VAS) at 24, 48, and 72 h postintervention was decreased in both groups compared with the baseline data; moreover, the observation group scored significantly lower than the control group on the VAS at each time point after the intervention (P < 0.05). The clinical efficacy at 24 h postintervention was not significantly different between the two groups (P > 0.05). In turn, the pain recurrence rate at 72 h postintervention was lower in the observation group compared with the control group (P < 0.05). Finally, the nursing satisfaction rate in the observation group was significantly higher than that observed in the control group (P < 0.05). No serious adverse reactions occurred during the treatment and the safety of treatment was high in both groups. CONCLUSION: Wrist-ankle acupuncture combined with pain nursing for treating urolithiasis with acute pain effectively alleviated the degree of pain and reduced the recurrence rate, which was worthy of clinical application.

Ethyl acetate extract of Gastrodia elata protects Caenorhabditis elegans from oxidative stress and amyloid ß peptide toxicity.

Gastrodia elata Blume is a traditional Chinese medicine with a long history, which has numerous pharmacological activities, such as anti-inflammation, anti-oxidation and protection of nerves. The present study investigated the regulatory effect of ethyl acetate extract of Gastrodia elata (EEGE) on the ß-amyloid (Aß) toxicity of Caenorhabditis elegans (C. elegans). First, the main components of EEGE were analyzed using high-performance liquid chromatography, and the total phenols, total flavonoids and total antioxidant capacity of EEGE were determined. Next, the regulation effect of EEGE on Aß-induced toxicity of C. elegans was evaluated through experiments on nematode paralysis, lifespan, oxidative and heat stress, locomotor ability, reproductive ability, reactive oxygen species (ROS) level, Aß aggregation test, malondialdehyde (MDA) level, catalase (CAT) activity and superoxide dismutase (SOD) activity. Finally, the mechanism of EEGE was elucidated using RNA sequencing (RNA-Seq) and the expression levels of related genes were verified using quantitative PCR. The present study revealed that the main components of EEGE included phosphorylated (p)-hydroxybenzyl alcohol, p-hydroxybenzaldehyde and 4,4'-dihydroxydiphenylmethane, possessing strong in vitro free radical scavenging and reducing abilities. In addition, after the intervention of EEGE, the paralysis of nematodes could be delayed, the survival time of the nematodes was prolonged, the survival rate of the nematodes under stress (high temperature and oxidation) conditions was improved, the activity capacity and reproductive capacity of the nematodes were improved, the activities of SOD and CAT were improved and the levels of ROS and MDA were reduced. Notably, EEGE directly inhibited Aß plaque aggregation in nematodes. RNA-Seq analysis showed that EEGE regulated metabolism and longevity-related genes, and these genes were regulated by the insulin/IGF-1 signaling (IIS) pathway. Therefore, the present study hypothesized that the regulatory mechanism of EEGE was significantly related to the IIS pathway. The present research results demonstrated that the protective effect of EEGE on transgenic C. elegans was to reduce Aß protein aggregation, improve the in vivo antioxidant level, effectively remove free radicals and to regulate the expression of genes related to IIS pathway, thereby reducing Aß-induced toxicity and delaying nematode paralysis.

Comparative Efficacy of Different Acupuncture-Related Therapies for Primary Tinnitus: A Systematic Review and Network Meta-Analysis Protocol.

Background: Acupuncture is considered as a potential treatment option for primary tinnitus, as there is a lack of conventional therapies with well-established efficacy. However, there are limited studies that compare the effectiveness of different acupuncture therapies. Thus, this systematic review and network meta-analysis protocol aims to compare the efficacy of various acupuncture-related therapies for primary tinnitus, and determine the optimal treatment. Methods: A comprehensive search of 10 representative databases will be conducted to identify eligible randomized controlled trials (RCTs) regarding multiple acupuncture-related therapies for primary tinnitus. Two independent researchers will extract data individually, and the methodological quality of each RCT will be assessed using Cochrane's risk of bias 2.0 tool. Standard pairwise meta-analysis and Bayesian network meta-analysis will be conducted, and WinBUGS V.1.4.3 and R 3.6.2 software will be adopted to synthesize network data and generate relevant graphs. Subgroup analyses, sensitivity analyses, and assessment of publication bias will be conducted as appropriate. Discussion: This study's results are anticipated to identify the optimal acupuncture technique for treating primary tinnitus, thereby providing evidence-based clinical decisions for patients and clinicians to select the most effective acupuncture treatment. Prospero Registration Number: CRD42023399621.

[Quality control mechanism of mitochondria by 3,4-dihydroxybenzaldehyde through OGT-PINK1 pathway].

Based on the O-GlcNAc transferase(OGT)-PTEN-induced putative kinase 1(PINK1) pathway, the mechanism of 3,4-dihydroxybenzaldehyde(DBD) on mitochondrial quality control was investigated. Middle cerebral artery occlusion/reperfusion(MCAO/R) rats were established. SD rats were randomized into sham operation group(sham), model group(MCAO/R), DBD-L group(5 mg·kg~(-1)), and DBD-H group(10 mg·kg~(-1)). After 7 days of administration(ig), MCAO/R was induced in rats except the sham group with the suture method. Twenty-four h after reperfusion, the neurological function and the percentage of cerebral infarct area were measured. Based on hematoxylin and eosin(HE) staining and Nissl staining, the pathological damage of cerebral neurons was examined. Then the ultrastructure of mitochondria was observed under the electron microscope, and the co-localization of light chain-3(LC3), sequestosome-1(SQSTM1/P62), and Beclin1 was further detected by immunofluorescence staining. It has been reported that the quality of mitochondria can be ensured by inducing mitochondrial autophagy through the OGT-PINK1 pathway. Therefore, Western blot was employed to detect the expression of OGT, mitophagy-related proteins PINK1 and E3 ubiquitin ligase(Parkin), and mitochondrial kinetic proteins dynamin-like protein 1(Drp1) and optic atrophy 1(Opa1). The results showed that MCAO/R group had neurological dysfunction, large cerebral infarct area(P<0.01), damaged morphological structure of neurons, decreased number of Nissl bodies, mitochondrial swelling, disappearance of mitochondrial cristae, decrease of cells with LC3 and Beclin1, rise of cells with P62(P<0.01), inhibited expression of OGT, PINK1, and Parkin, up-regulated expression of Drp1, and down-regulated expression of Opa1 compared with the sham group(P<0.01). However, DBD improved the behavioral deficits and mitochondrial health of MCAO/R rats, as manifested by the improved morphology and structure of neurons and mitochondria and the increased Nissl bodies. Moreover, DBD increased cells with LC3 and Beclin1 and decreased cells with P62(P<0.01). In addition, DBD promoted the expression of OGT, PINK1, Parkin, and Opa1 and inhibited the expression of Drp1, enhancing mitophagy(P<0.05, P<0.01). In conclusion, DBD can trigger PINK1/Parkin-mediated brain mitophagy through the OGT-PINK1 pathway, which plays a positive role in maintaining the health of the mitochondrial network. This may be a mitochondrial therapeutic mechanism to promote nerve cell survival and improve cerebral ischemia/reperfusion injury.

Proteomics and transcriptomics explore the effect of mixture of herbal extract on diabetic wound healing process.

BACKGROUND: The annual incidence of diabetic foot ulcers (DFUs) has been reported to vary from 0.2% to 11% in diabetes-specific clinical settings and less than 0.1% to 8% in community- and population-based cohorts. According to the International Diabetes Foundation, approximately 40 million to 60 million people worldwide are affected by DFUs, and a recent meta-analysis indicates a global prevalence of 6.3% among adults with diabetes, or about 33 million individuals. The cost of diabetes care is significant, amounting to $273 billion in direct and $90 billion in indirect expenses annually, in America. Foot complications in diabetes care excess annual expenditures ranging from 50% to 200% above the baseline cost of diabetes-related care. The cost of advanced-stage ulcers can be more than $50,000 per wound episode, and the direct expenses of major amputation are even higher. DFUs can be treated using various methods, including wound dressings, antibiotics, pressure-off loading, skin substitutes, stem cells, debridement, topical oxygen therapy, gene therapy and growth factors. For severe DFUs patients are at risk of amputation if treatment is not timely or appropriate. Amputating limbs not only causes physical pain to patients, but also brings economic burden due to lost productivity, and decreased employment linked to DFUs. Currently, long-term use of local antibiotics in clinical practice is prone to induce drug resistance, while growth factors do not effectively inhibit bacterial growth and control inflammation in wounds. Stem cell and gene therapies are still in the experimental stage. The method of local debridement combined with negative pressure therapy is expensive. Therefore, we urgently need an affordable, non-surgical method to treat diabetic ulcers. Extracts of bark of Bauhinia purpurea, Paeoniae rubrae, Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., Acorus calamus L, and Radix Angelicae biseratae have been used as traditional remedies to treat inflammation-related diseases and cutaneous wounds due to their anti-inflammatory properties and their ability to promote vascular renewal. However, there have been few studies on the mixture of these five herbal extracts on diabetic wound healing. PURPOSE: This study was designed to assess the healing effect of a mixture of five aforementioned herbal extracts on diabetic ulcer wounds in rats, and to reveal the potential mechanisms behind any potential wound healing using transcriptomics and proteomics. STUDY DESIGN: We designed the experiment to explore the effects of five herbal extracts on diabetic wound healing process through in vivo experiments and to investigate the underlying mechanisms through proteomics and transcriptomics. METHODS: We used a mixture of five aforementioned herbal extract to treat rat model of diabetic established by intraperitoneal injection of streptozotocin, and a 2 × 2 cm round full-thickness skin defect was created on the back of the rat. Staphylococcus aureus (1 ml of 1.5 × 109 cfu/ml) was evenly applied to the wound. The wound was then observed for 72 h. The infected ulcer model of diabetic rats was considered to be successfully established if the wound was found to be infected with S. aureus. According to different medications, the rats were divided into three groups, namely mixture of herbal extract (MHE), Kangfuxin solution (KFS) and control (Ctrl). The effects of the medicine on wound healing were observed. HE staining and Masson staining were performed to evaluate the histopathological changes and collagen synthesis. IHC staining was used to assess the neovascularization, and M2 macrophage proliferation was determined by immunofluorescence staining. Proteomic and transcriptomic studies were performed to explore potential mechanism of five herbal extracts to promote wound healing. UHPLC-QE-MS was performed to identify the chemical composition of mixture of herbal extract. RESULTS: The study show that the mixed herbal extract promotes angiogenesis, proliferation of M2 macrophages, and collagen synthesis. Transcriptomics showed that rno-miR-1298, rno-miR-144-5p, and rno-miR-92a-1-5p are vital miRNAs which also play a significant role in role in regulating wound healing. Proteomics results showed that the following proteins were important in wounds treated with MHE: Rack1, LOC100362366, Cops2, Cops6, Eif4e, Eif3c, Rpl12, Srp54, Rpl13 and Lsm7. Autophagy, PI3-Akt and mTOR signaling pathways were enriched after treatment with MHE compared to other groups. CONCLUSION: Herein, we have shown that MHE containing extracts of bark of Bauhinia purpurea, P. rubrae, A. dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., A. calamus L, and R. A. biseratae has significant wound healing effects in the diabetic ulcer wound rat model. These results suggest that local application of MHE in diabetic wounds can accelerate the wound healing process. Moreover, in vivo experiments revealed that the diabetic wound healing process was primarily mediated by angiogenesis and M2 macrophage transition. Therefore, this study may provide a promising and non-surgical therapeutic strategy to accelerate diabetic wound healing, thereby decreasing the number of limb amputations in diabetic patients.

Biomass partitioning and ionomics of Macadamia with high manganese and low phosphorus concentrations.

Knowledge of the ionome of plant organs helps us understand a plant's nutritional status. However, the ionome of Macadamia (Proteaceae), which is an important nut-producing tree, remains unknown. We aimed to characterise the allocation of biomass and nutrient-partitioning patterns in three macadamia genotypes. We excavated 15 productive trees (three cultivars at 21years of age; two cultivars at 16years of age) in an orchard. Biomass, nutrient concentrations, and contents of roots, stems, branches, and leaves were analysed. Dry weight of roots, stems, branches and leaves accounted for 14-20%, 19-30%, 36-52%, and 12-18% of total plant weight, respectively. No significant difference was found in the total biomass among the cultivars at the same age. Compared with most crop plants, macadamia had low phosphorus (P) concentrations in all organs (<1gkg-1 ), and low leaf zinc (Zn) concentration (8mgkg-1 ). In contrast, macadamia accumulated large amounts of manganese (Mn), with a 20-fold higher leaf Mn concentration than what is considered sufficient for crop plants. Leaves exhibited the highest nutrient concentrations, except for iron and Zn, which exhibited the highest concentrations in roots. The organ-specific ionomics of Macadamia is characterised by low P and high Mn concentrations, associated with adaptation to P-impoverished habitats.

Cooperative phototherapy based on bimodal imaging guidance for the treatment of uveal melanoma.

BACKGROUND: Uveal melanoma (UM) is adults' most common primary intraocular malignant tumor, prone to metastasis and high mortality. Eyeball enucleation commonly used in the clinic will lead to permanent blindness and mental disorders. Thus, new methods are urgently needed to diagnose and treat UM early to preserve patients' vision. METHODS AND RESULTS: Herein, multifunctional nanoparticles (NPs) were synthesized by loading chlorin e6 (Ce6) in poly-lactic-co-glycolic acid (PLGA) NPs and wrapping FeIII-tannic acid (FeIII-TA) on the outside (FeIII-TA/PLGA/Ce6, designated as FTCPNPs). Then, the synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) antitumor effects of FTCPNPs excited by near-infrared (NIR) laser were evaluated. Moreover, we verified the mechanism of synergistic PTT/PDT leading to mitochondrial dysfunction and inducing tumor cell apoptosis. Additionally, FTCPNPs can be used as excellent magnetic resonance (MR)/photoacoustic (PA) imaging contrast agents, enabling imaging-guided cancer treatment. Finally, The NPs have good biological safety. CONCLUSION: This noninvasive NIR light-triggered cooperative phototherapy can easily penetrate eye tissue and overcome the disadvantage of limited penetration of phototherapy. Therefore, cooperative phototherapy is expected to be used in fundus tumors. This treatment model is applied to UM for the first time, providing a promising strategy and new idea for integrating the diagnosis and treatment of UM.

Comprehensive Microbiome and Metabolome Analyses Reveal the Medicinal Components of Paeonia lactiflora.

Paeonia lactiflora Pall. is not only a traditional ornamental plant, but also an important medicinal plant. Currently, some P. lactiflora cultivars are used for ornamental purposes, but their potential medicinal value is ignored. To explore the medicinal potential of the ornamental varieties, the medicinal cultivar 'Hangbaishao' (HS) and the ornamental cultivar 'Zifengyu' (ZFY) were selected, and microbiome and metabolome analyses were performed to compare the composition of the endophytes and metabolites in the roots. The diversity and abundance of bacteria were not significantly different between HS and ZFY; however, the diversity and abundance of endophytic fungi in the ornamental cultivar ZFY were much higher than those in the medicinal cultivar HS. The flavonoids and phenolic acid contents of the ornamental cultivar ZFY were significantly higher than those of the medicinal cultivar HS, indicating that ZFY has medicinal value. The differences in root endophytes between HS and ZFY may lead to differences in phenolic acids and flavonoids. To explore the relationship between endophytes and the accumulation of phenolic acids and flavonoids, a joint analyses of the microbiome and metabolome were performed. The key bacterium, Ruminococcaceae bacterium GD7, led to the accumulation of phenolic acids and flavonoids in the ZFY. This study contributes to future research on the potential medicinal value of ornamental P. lactiflora and provides a new approach for realizing the 'dual use of medicine and appreciation' of P. lactiflora.

Therapeutic potential of artemisinin and its derivatives in managing kidney diseases.

Artemisinin, an antimalarial traditional Chinese herb, is isolated from Artemisia annua. L, and has shown fewer side effects. Several pieces of evidence have demonstrated that artemisinin and its derivatives exhibited therapeutic effects on diseases like malaria, cancer, immune disorders, and inflammatory diseases. Additionally, the antimalarial drugs demonstrated antioxidant and anti-inflammatory activities, regulating the immune system and autophagy and modulating glycolipid metabolism properties, suggesting an alternative for managing kidney disease. This review assessed the pharmacological activities of artemisinin. It summarized the critical outcomes and probable mechanism of artemisinins in treating kidney diseases, including inflammatory, oxidative stress, autophagy, mitochondrial homeostasis, endoplasmic reticulum stress, glycolipid metabolism, insulin resistance, diabetic nephropathy, lupus nephritis, membranous nephropathy, IgA nephropathy, and acute kidney injury, suggesting the therapeutic potential of artemisinin and its derivatives in managing kidney diseases, especially the podocyte-associated kidney diseases.

[Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats].

OBJECTIVE: To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior. METHODS: Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined. RESULTS: Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group. CONCLUSION: Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.