Composition of Sphagnum palustre L. extracts using different extraction methods.

Sphagnum palustre L. is a Chinese herbal medicine with a long history, however, few studies have been performed on its chemical composition and active effects. In this study, we investigated the composition and antibacterial and antioxidant capacities of extracts obtained from Sphagnum palustre L. phytosomes extracted with conventional solvents (water, methanol, and ethanol) and two different hydrogen bond donors (citric acid and 1,2-propanediol) modified with choline chloride-type deep eutectic solvents (DESs). The results show that Sphagnum palustre extracts contained 253 compounds, including citric acid, ethyl maltol, and thymol. The highest total phenolic content (TPC) was obtained with a DES extraction method combining 1,2-propanediol and choline chloride (39.02 ± 7.08 mg gallic acid equivalent/g dried weight (DW). This shows the composition of Sphagnum palustre as a natural product and the application of DESs in the extraction of active ingredients, demonstrating the potential of peat moss extracts in cosmetics and health products.

Dual-stimuli responsive smart nanoprobe for precise diagnosis and synergistic multi-modalities therapy of superficial squamous cell carcinoma.

BACKGROUND: Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects. RESULTS: Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them. CONCLUSION: The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.

Comparative transcriptomes of nine tissues for the Heilongjiang brown frog (Rana amurensis).

The Heilongjiang brown frog (Rana amurensis) is widely used in traditional Chinese medicine. In particular, the oviduct and skin have been developed into various health products. However, limited numbers of complete genomes of amphibian species have been reported, excluding the Heilongjiang brown frog. Here, the transcriptomes of 45 samples from the liver, spleen, heart, ovaries, thigh muscles, skin, oviduct, stomach and intestine of five Heilongjiang brown frog were reassembled and analyzed. A total of 1,085,532 unigenes with an average length of 676.6 bp and N50 of 722 bp were obtained. Comparative transcriptomics of different tissues detected tissue-specific expression. There were 3248 differentially expressed genes (DEGs) in the ovary, and the number of unique DEGs between the ovary and spleen was the largest. The results of DEGs enrichment showed there were many pathways and items related to protein synthesis and metabolism in the oviduct. The DEGs of the skin were enriched with many bacterial defense items, indicating that there were a large number of antimicrobial peptides in the skin. Thus, these were suitable as biological sources for the development and extraction of antimicrobial peptides. Through the assembly of transcriptome sequencing data and functional annotation of the Heilongjiang brown frog genome, this study provides reference materials for further exploring and utilizing functional gene resources of frogs and lays a foundation for medical research and the development of new products.

Toxin-Antitoxin Systems Alter Adaptation of Mycobacterium smegmatis to Environmental Stress.

Toxin-antitoxin (TA) systems are ubiquitous genetic elements in prokaryotes, but their biological importance is poorly understood. Mycobacterium smegmatis contains eight putative TA systems. Previously, seven TAs have been studied, with five of them being verified as functional. Here, we show that Ms0251-0252 is a novel TA system in that expression of the toxin Ms0251 leads to growth inhibition that can be rescued by the antitoxin Ms0252. To investigate the functional roles of TA systems in M. smegmatis, we deleted the eight putative TA loci and assayed the mutants for resistance to various stresses. Deletion of all eight TA loci resulted in decreased survival under starvation conditions and altered fitness when exposed to environmental stresses. Furthermore, we showed that deletion of the eight TA loci decreased resistance to phage infection in Sauton medium compared with the results using 7H10 medium, suggesting that TA systems might have different contributions depending on the nutrient environment. Furthermore, we found that MazEF specifically played a dominant role in resistance to phage infection. Finally, transcriptome analysis revealed that MazEF overexpression led to differential expression of multiple genes, including those related to iron acquisition. Altogether, we demonstrate that TA systems coordinately function to allow M. smegmatis to adapt to changing environmental conditions. IMPORTANCE Toxin-antitoxin (TA) systems are mechanisms for rapid adaptation of bacteria to environmental changes. Mycobacterium smegmatis, a model bacterium for studying Mycobacterium tuberculosis, encodes eight putative TA systems. Here, we constructed an M. smegmatis mutant with deletions of all eight TA-encoding genes and evaluated the resistance of these mutants to environmental stresses. Our results showed that different TA systems have overlapping and, in some cases, opposing functions in adaptation to various stresses. We suggest that complementary TA modules may function together to regulate the bacterial stress response, enabling adaptation to changing environments. Together, this study provides key insights into the roles of TA systems in resistance to various environmental stresses, drug tolerance, and defense against phage infection.

A network pharmacology-based exploration of the active compounds and potential drug targets of Si-Jun-Zi decoction in the treatment of cutaneous squamous cell carcinoma.

Background: Cutaneous squamous cell carcinoma (cSCC), a kind of skin cancer with high rates of morbidity and mortality, occurs frequently in the clinic. Although early surgical treatment can achieve good results, there is no effective prevention and treatment for the recurrence and metastasis of cSCC. As a useful resource to protect humans from disease, traditional Chinese medicine (TCM) has been adopted by clinicians for thousands of years. Methods: In this study, we collected a Chinese medicine formula and then employed a data mining method to analyze drug combinations of Si-Jun-Zi (SJZ) decoction. Multiple databases were used in this study to predict various ingredients, compounds, and their targets in the decoction. The potential targets of cSCC were also obtained from the database in the same way. In addition, as bioinformatics analysis methods, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used in our research as supplementary means to network pharmacology. Finally, we used ultra-performance liquid chromatography (UPLC) fingerprinting to analyze the effective components of the TCM decoction. Results: We detected 559 active compounds from Ginseng, Largehead Atractylodes, India Bread, and Glycyrrhiza Inflata, and selected 136 molecules under specific conditions. The mechanisms of the TCM formula were illustrated by the network pharmacology, such as compounds-herb network, compounds-target network, disease-target network, and target-target interaction network, as well as characteristics of the TCM. Then, GO analysis and KEGG analysis were performed on the compounds in the network using multiple methods of data mining and bioinformatics, and 10 candidate targets were identified. In addition, the UPLC fingerprinting method was used to analyze the components of SJZ decoction. Conclusions: Network pharmacology was performed to investigate the characteristics and mechanism of SJZ decoction, and a bioinformatics method was used to analyze the relationship between the effective compounds of the SJZ TCM decoction and cSCC-related specific targets and pathways, to find a variety of candidate compounds with multi-target activity.

Effect of Executive Dysfunction on Posture Control and Gait after Stroke.

OBJECTIVE: The purpose of the study was to observe the effects of executive dysfunction (ED) on gait and postural control during walking after stroke. METHODS: In this study, 34 subjects with stroke and ED (8 women and 26 men; age, 55.41 ± 7.89 years; time since stroke onset, 1.3 ± 0.12 months) were recruited. Stroop color-word test (SCWT), 10-meter walk test (10MWT), timed-up-and-go test (TUGT), and gait analysis were evaluated. The correlation among the correct number of Stroop tasks (SCWT-C), the number of time-consuming tasks (SCWT-T), the amount of interference (SIE-M and SIE-T) and posture control, and gait-related parameters was analyzed. RESULTS: The results indicated that SCWT-C was negatively correlated with 10MWT, TUGT, and bilateral symmetry (P < 0.05). However, there was no significant correlation between SCWT-C and stride (P > 0.05). A significant negative correlation was seen between SCWT-C and bilateral symmetry (P < 0.05). There was no significant correlation between SCWT-T and stride (P > 0.05). SCWT-T was positively correlated with TUGT, 10MWT, and bilateral symmetry (P < 0.05). SIE-T was positively correlated with TUGT and bilateral symmetry (P < 0.05). There was no significant correlation between SIE-T and 10MWT or stride (P > 0.05). SIE-M was positively correlated with TUGT and bilateral symmetry (P < 0.05). There was no significant correlation between SIE-T and 10MWT or stride (P > 0.05). CONCLUSIONS: ED is closely related to the decline in postural control and the occurrence of falls. In the early phases of stroke rehabilitation, physiotherapists should focus on the patients' executive function to accelerate the recovery of postural control.

Yiqi Jiedu Huayu Decoction Alleviates Renal Injury in Rats With Diabetic Nephropathy by Promoting Autophagy.

Diabetic nephropathy (DN), a common microvascular complication of diabetes, is one of the main causes of end-stage renal failure (ESRD) and imposes a heavy medical burden on the world. Yiqi Jiedu Huayu decoction (YJHD) is a traditional Chinese medicine formula, which has been widely used in the treatment of DN and has achieved stable and reliable therapeutic effects. However, the mechanism of YJHD in the treatment of DN remains unclear. This study aimed to investigate the mechanism of YJHD in the treatment of DN. Sprague-Dawley rats were randomly divided into a normal control group, a diabetic group, an irbesartan group, and three groups receiving different doses of YJHD. Animal models were constructed using streptozotocin and then treated with YJHD for 12 consecutive weeks. Blood and urine samples were collected during this period, and metabolic and renal function was assessed. Pathological kidney injury was evaluated according to the kidney appearance, hematoxylin-eosin staining, Masson staining, periodic-acid Schiff staining, periodic-acid Schiff methenamine staining, and transmission electron microscopy. The expression levels of proteins and genes were detected by immunohistochemistry, western blotting, and real-time qPCR. Our results indicate that YJHD can effectively improve renal function and alleviate renal pathological injury, including mesangial matrix hyperplasia, basement membrane thickening, and fibrosis. In addition, YJHD exhibited podocyte protection by alleviating podocyte depletion and morphological damage, which may be key in improving renal function and reducing renal fibrosis. Further study revealed that YJHD upregulated the expression of the autophagy-related proteins LC3II and Beclin-1 while downregulating p62 expression, suggesting that YJHD can promote autophagy. In addition, we evaluated the activity of the mTOR pathway, the major signaling pathway regulating the level of autophagy, and the upstream PI3K/Akt and AMPK pathways. YJHD activated the AMPK pathway while inhibiting the PI3K/Akt and mTOR pathways, which may be crucial to its promotion of autophagy. In conclusion, our study shows that YJHD further inhibits the mTOR pathway and promotes autophagy by regulating the activity of the PI3K/Akt and AMPK pathways, thereby improving podocyte injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research into YJHD.

Near-Infrared Light Laser-Triggered Release of Doxorubicin and Sorafenib from TemperatureSensitive Liposomes for Synergistic Therapy of Hepatocellular Carcinoma.

Chemotherapy of hepatocellular carcinoma (HCC) is facing drug resistance, which leads to unsatisfactory therapeutic effect. Thus, a combination therapy using multiple drugs may overcome this challenge. The current study aims to realize a synergistic chemotherapy of HCC by using a near-infrared light (NIR) responsive nanocarrier to co-deliver the chemotherapeutic drug Doxorubicin (DOX) and molecular targeting agent Sorafenib (SF). The nanocarrier, which could effectively load DOX in its aqueous core while SF and IR-780 in its lipid bilayer, is fabricated from a temperature-sensitive liposome (TSL) modified with PF127. An efficient SF and DOX co-loading was achieved, and meanwhile the effective photothermal conversion of IR-780 under NIR laser may cause a disassembly of the liposome structure which may trigger a rapid drug release in tumor site, greatly boosting the synergetic chemotherapeutic effect. The NIR laser-triggered drug release and the synergistic anti-tumor effect were evaluated both in cell and animal experiments, which revealed that the PF127-modified TSL is a potent nanoplatform to improve the HCC treatment through co-delivering a drug combination.

Continuous theta burst stimulation provides neuroprotection by accelerating local cerebral blood flow and inhibiting inflammation in a mouse model of acute ischemic stroke.

Acute ischemic stroke is a leading cause of disability with limited therapeutic options. Continuous theta burst stimulation (cTBS) has recently been shown to be a promising noninvasive therapeutic strategy for neuroprotection in ischemic stroke patients. Here, we investigated the protective effects of cTBS following acute infarction using a photothrombotic stroke (PTS) model in the right posterior parietal cortex (PPC) of C57BL/6 mice. Treatment with cTBS resulted in a reduction in the volume of the infarct region and significantly increased vascular diameter and blood flow velocity in peri-infarct region, as well as decreased the numbers of calcium binding adapter molecule 1 (Iba-1)-positive microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes. Moreover, the number of CD16/32 positive microglia was decreased, whereas the number of CD206 positive microglia was increased. In addition, performance in a water maze task was significantly improved. These results indicated that cTBS protected against PPC infarct region, leading to an improvement in spatial cognitive function, possibly as a result of changes to cerebral microvascular function and inflammatory responses.

Phasic GABA signaling mediates the protective effects of cTBS against cerebral ischemia in mice.

Continuous theta burst stimulation (cTBS) has been widely recognized as a therapeutic treatment for ischemic stroke, but the underlying mechanism is still elusive. Here, we investigated the protective effects of cTBS in the posterior parietal cortex during the chronic phase of stroke in the photothrombotic ischemic model. Infarction volume and neuron excitability in the peri-infarct area were assessed using immunohistochemistry and whole-cell patch-clamp. Spatial cognitive function was measured using the Morris water maze. Gamma-Amino butyric acid (GABA) interneurons were responsive to cTBS, and cTBS induced elevated phasic inhibition rather than tonic inhibition. Given that GABA-A-mediated phasic inhibition was elevated during the chronic phase of ischemic stroke for 30 days and was beneficial for stroke recovery, we investigated the therapeutic potential of cTBS in promoting functional recovery and found that the elevated phasic inhibition by cTBS improved spatial cognitive function in the photothrombotic stroke mouse model with induction in the posterior parietal cortex. Our study indicates the mechanism by which cTBS may modify the excitability of the brain cortex and provides novel insight into the potential of cTBS to protect against neuronal dysfunction in ischemic stroke.

Aromatic-Turmerone Attenuates LPS-Induced Neuroinflammation and Consequent Memory Impairment by Targeting TLR4-Dependent Signaling Pathway.

SCOPE: Curcuma longa (turmeric) is a folk medicine in South and Southeast Asia, which has been widely used to alleviate chronic inflammation. Aromatic-turmerone is one of the main components abundant in turmeric essential oil. However, little information is available from controlled studies regarding its biological activities and underlying molecular mechanisms against chronic inflammation in the brain. In the current study, we employed a classical LPS model to study the effect and mechanism of aromatic-turmerone on neuroinflammation. METHODS AND RESULTS: The effects of aromatic-turmerone were studied in LPS-treated mice and BV2 cells. The cognitive function assays, protein analyses, and histological examination were performed. Oral administration of aromatic-turmerone could reverse LPS-induced memory disturbance and normalize glucose intake and metabolism in the brains of mice. Moreover, aromatic-turmerone significantly limited brain damage, through inhibiting the activation of microglia and generation of inflammatory cytokines. Further study in vitro revealed that aromatic-turmerone targeted Toll-like receptor 4 mediated downstream signaling, and lowered the release of inflammatory mediators. CONCLUSION: These observations indicate that aromatic-turmerone is effective in preventing brain damage caused by neuroinflammation and may be useful in the treatment of neuronal inflammatory diseases.

[Study on effect of total coumarins from Urtica dentata on dextran sulfate sodium-induced colitis in mice].

OBJECTIVE: To study the effect of total coumarins (TC) from Urtica dentata on dextran sulfate sodium (DSS)-induced colitis in mice. METHOD: The colitis model was established by administering DSS. Having been treated with TC, their body weight was determined. Concentrations of IL-6, IL-10, TGF-beta1 and IFN-gamma were monitored by ELISA. Colon samples were collected for the histopathological examination. Western blot was used to detect TLR4 and NF-kappaB protein expression in colonic tissues. RESULT: TCs from U. dentata effectively controlled the body weight loss of mice with colitis, down-regulated the concentration of IL-6 and IFN-gamma and increased the suppressive cytokines IL-10 and TGF-beta1 in the serum. Additionally, TC alleviated the mucosal damage and decreased the expressions of TLR4 and NF-kappaB in colonic tissues. CONCLUSION: TCs from U. dentata shows the anti-inflammatory effect on colitis in mice by reducing the expressions of TLR4 and NF-kappaB in colonic tissues and regulating pro-and anti-inflammatory cytokines.

Treatment of 36 Cases of Infantile Enuresis by Acupuncture / 针灸推拿医学（英文版）

Treated 36 cases of infantile enuresis by acupuncturing Zuyunganqu (Foot Motor Sensory Area),Guanyuan (CV 4), Qihai (CV 6), Zhongwan (CV 12),Zusanli (ST 36), Yinlingquan (SP 9), Pishu (BL 20),Weishu (BL 21) and Shenshu (BL 23). After two courses,29 cases were cured, 5 cases were improvement and 2cases were no effect.