Ethnobotanical study on medicinal plants used by the Yi people in Xiaoliangshan, Yunnan Province, SW China.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yi people in the Xiaoliangshan region in southwest China have a unique practice of combining ritual treatment and traditional medicine to care for patients. Despite increasing urbanization in the area, they have managed to preserve their distinctive lifestyle and extensive knowledge of traditional medicinal plants, setting them apart from other regions. However, there is a lack of systematic documentation on the knowledge of traditional medicinal plants used by the Yi people in Xiaoliangshan. AIM OF THE STUDY: This research aims to achieve the following objectives: 1. Document the diversity of medicinal plants used by the Yi people and explore their therapeutic usages. 2. Evaluate and analyze the main types of diseases with a high incidence in the local area and identify the types of medicinal plants used to treat these diseases. 3. Explore the underlying geographical and human factors influencing both disease prevalence and medicinal plant usage. METHODS: Ethnobotanical research methods were used to record and analyze the medicinal plants used by the Yi in Xiaoliangshan. Experts identified all plant specimens collected during ethnobotanical field surveys. The types of diseases treated by medicinal plants were classified according to the International Classification of Primary Care -2nd. RESULTS: A total of 125 medicinal plants were recorded after interviewing 193 participants. Of the medicinal plants identified, those with over 100 use reports were Paris polyphylla (202 use reports), Taxillus sutchuenensis (183), Artemisia indica (149), and Papaver somniferum (113). A total of 14 disease categories were recorded, with those related to the following categories having higher Informant Consensus factor values (ICF ≥0.85): Pregnancy, Childbearing, Family Planning, General and Unspecified, Urological, Respiratory, Musculoskeletal, and Skin. The highest quantity of medicinal plants is utilized to improve specific diseases and health problems, namely those related to Digestion, Skin, and Musculoskeletal. Fewer plant species were utilized for diseases or health issues associated with Eyes, Psychological, or Pregnancy, Childbearing, and Family Planning. The use reports from the informants also revealed how some medicinal plants are used to treat a variety of diseases or health issues. For instance, Malva pusilla is used for inducing abortion, treating postpartum hemorrhage, and joint sprains; Artemisia indica is used for treating malaria; Argentina lineata is used to remedy tuberculosis and malaria. Taxillus sutchuenensis is used for dealing with cold, pneumonia, and other ailments. CONCLUSIONS: The Yi people in Xiaoliangshan have a rich knowledge of traditional medicinal plants. Decoction and wine brewing are the most common processing methods used for these plants, which are utilized to treat a wide range of diseases. The characteristics of the medicinal use of the Yi people reflects the alpine mountainous environment in which they live, and their medical practices are closely related to traditional healing culture. This study enhances our understanding of the Yi traditional medicine via documentation and offers a valuable reference for future research and the development of new drugs.

Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3-ITD: A multicenter phase 2 study.

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3-internal tandem duplication (FLT3-ITD) respond infrequently to salvage chemotherapy. OBJECTIVE: To investigate the efficacy of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as a salvage therapy in this population. METHODS: This multicenter, single-arm, phase 2 study was conducted at 12 hospitals across China. Eligible patients had R/R AML with FLT3-ITD (aged 18-65 years) who were treated with VAH. The primary endpoint was composite complete remission (CRc) after two cycles. Secondary outcomes included the overall response rate (ORR), safety, and survival. RESULTS: Between July 9, 2020, and March 19, 2022, 58 patients were assessed for eligibility, 51 of whom were enrolled. The median patient age was 47 years (interquartile range [IQR] 31-57). CRc was 76.5% with ORR of 82.4%. At a median follow-up of 17.7 months (IQR, 8.7-24.7), the median duration of CRc was not reached (NR), overall survival was 18.1 months (95% confidence interval [CI], 11.8-NR) and event-free survival was 11.4 months (95% CI, 5.6-NR). Grade 3 or 4 adverse events occurring in ≥10% of patients included neutropenia in 47 (92.2%), thrombocytopenia in 41 (80.4%), anemia in 35 (68.6%), febrile neutropenia in 29 (56.9%), pneumonia in 13 (25.5%), and sepsis in 6 (11.8%) patients. Treatment-related death occurred in two (3.9%) patients. CONCLUSIONS: The sorafenib plus VAH regimen was well tolerated and highly active against R/R AML with FLT3-ITD. This regimen may be a suitable therapeutic option for this population, but larger population trials are needed to be explored. TRIAL REGISTRATION: Clinical Trials Registry: NCT04424147.

An ethnobotanical study of wild edible plants used by the Tibetan in the Rongjia River Valley, Tibet, China.

BACKGROUND: Wild edible plants (WEPs) play a crucial role in communities with limited communication with the outside world, where unstable factors, such as poor food supply and insufficient access to timely nutritional supplementation, are common, as in the Himalayan region. To document the traditional knowledge of WEPs and explore their significance for communities with minimal global economic exchange, an ethnobotanical study was conducted in the town of Rongjia, which lies in a narrow valley near Mount Everest, Tibet, China. METHODS: This ethnobotanical study was conducted in three villages in the Rongjia River Valley between August 2021 and June 2023. Semi-structured interviews and participatory observations were used to collect information on WEPs. The fieldwork was performed with the assistance of local guides. Voucher specimens were collected from each documented plant species for taxonomic identification. We used the use report (UR) and relative frequency of citations (RFC) to evaluate the comprehensive utilization value of WEPs. RESULTS: We interviewed 161 informants who provided us with 2499 use reports. We collected 50 WEPs belonging to 28 families and 42 genera used by the Tibetan people in the Rongjia River Valley. WEPs are used in vegetables, fruits, seasonings, healthcare foods, substitute grains, and beverages. Wild vegetables were the most commonly used, followed by wild fruits. Leaves were the most commonly consumed part of the plant. The three most important WEPs ordered by RFC values were Rosa sericea var. glandulosa Osmaston (RFC = 0.76), Zanthoxylum bungeanum Maxim. (RFC = 0.75), and Urtica hyperborea Jacquem. ex Wedd. (RFC = 0.71). Other than that, we also document some of WEPs used in the past. Arisaema erubescens Schott, Pinellia ternata (Thunb.) Makino, and Satyrium nepalense var. ciliatum (Lindl.) Hook. f. used to serve as important substitute grains, are no longer in use, however, they remain vivid in the memories of older people. CONCLUSIONS: WEPs included wild vegetables, fruits, seasonings, healthcare food, and substitute grains for Tibetan people in the Rongjia River Valley. Some WEPs have become important cultural symbols for older people, which can help in understanding the relationship between plants and local people in the past. In addition, WEPs can increase the resilience of local people living in remote areas when facing sudden destabilizing events in future. This is the significance of WEPs for communities with minimal global economic exchange. Therefore, we suggest that future studies focus more on WEPs in communities with limited communication with the world to improve their resilience.

[Research progress in treatment of Sjögren's syndrome by traditional Chinese medicine].

Sj9gren's syndrome(SS) is an autoimmune disease with glandular dysfunction caused by the massive infiltration of the exocrine glands by lymphocytes. The pathogenesis of this disease is related to the chronic inflammatory response of the exocrine glands due to excessive activation of B cells and T cells. In addition to dry mouth and eyes, SS can also cause damage to other organs and systems in the human body, seriously affecting the quality of life of patients. Traditional Chinese medicine(TCM) has definite clinical efficacy in the treatment of SS as it can alleviate symptoms and regulate immune disorders without causing adverse reactions, demonstrating high safety. This paper reviews the current status of preclinical and clinical trials about the TCM treatment of SS in the past decade. TCM mainly mitigates SS symptoms such as dry mouth, dry eyes, dry skin, and joint pain and improves the prognosis and quality of life of patients by regulating the abnormally activated B cells and T cells, inhibiting the autoimmune response, restoring the balance between pro-inflammatory and anti-inflammatory cytokines, and reducing the pathological damage caused by immune complexes to exocrine glands and joints in SS patients.

Allomelanin-based biomimetic nanotherapeutics for orthotopic glioblastoma targeted photothermal immunotherapy.

Immune checkpoint blockade (ICB) therapy has shown great potential in the treatment of malignant tumors, but its therapeutic effect on glioblastoma (GBM) is unsatisfactory because of the low immunogenicity and T cell infiltration, as well as the presence of blood-brain barrier (BBB) that blocks most of ICB agents to the GBM tissues. Herein, we developed a biomimetic nanoplatform of AMNP@CLP@CCM for GBM-targeted photothermal therapy (PTT) and ICB synergistic therapy by loading immune checkpoint inhibitor CLP002 into the allomelanin nanoparticles (AMNPs) and followed by coating cancer cell membranes (CCM). The resulting AMNP@CLP@CCM can successfully cross the BBB and deliver CLP002 to GBM tissues due to the homing effect of CCM. As a natural photothermal conversion agent, AMNPs are used for tumor PTT. The increased local temperature by PTT not only enhances BBB penetration but also upregulates the PD-L1 level on GBM cells. Importantly, PTT can effectively stimulate immunogenic cell death to induce tumor-associated antigen exposure and promote T lymphocyte infiltration, which can further amplify the antitumor immune responses of GBM cells to CLP002-mediated ICB therapy, resulting in significant growth inhibition of the orthotopic GBM. Therefore, AMNP@CLP@CCM has great potential for the treatment of orthotopic GBM by PTT and ICB synergistic therapy. STATEMENT OF SIGNIFICANCE: The effect of ICB therapy on GBM is limited by the low immunogenicity and insufficient T-cell infiltration. Here we developed a biomimetic nanoplatform of AMNP@CLP@CCM for GBM-targeted PTT and ICB synergistic therapy. In this nanoplatform, AMNPs are used as both photothermal conversion agents for PTT and nanocarriers for CLP002 delivery. PTT not only enhances BBB penetration but also upregulates the PD-L1 level on GBM cells by increasing local temperature. Additionally, PTT also induces tumor-associated antigen exposure and promotes T lymphocyte infiltration to amplify the antitumor immune responses of GBM cells to CLP002-mediated ICB therapy, resulting in significant growth inhibition of the orthotopic GBM. Thus, this nanoplatform holds great potential for orthotopic GBM treatment.

Zinc Deficiency Exacerbates Behavioral Impediments and Dopaminergic Neuron Degeneration in a Mouse Model of Parkinson Disease.

BACKGROUND: Circulating zinc (Zn) concentrations are lower than normal in patients with Parkinson disease (PD). It is unknown whether Zn deficiency increases the susceptibility to PD. OBJECTIVES: The study aimed to investigate the effect of dietary Zn deficiency on behaviors and dopaminergic neurons in a mouse model of PD and to explore potential mechanisms. METHODS: Male C57BL/6J mice aged 8-10 wk were fed Zn adequate (ZnA; 30 µg/g) or Zn deficient (ZnD; <5 µg/g) diet throughout the experiments. Six weeks later 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected to generate the PD model. Controls were injected with saline. Thus, 4 groups (Saline-ZnA, Saline-ZnD, MPTP-ZnA, and MPTP-ZnD) were formed. The experiment lasted 13 wk. Open field test, rotarod test, immunohistochemistry, and RNA sequencing were performed. Data were analyzed with t-test, 2-factor ANOVA, or Kruskal-Wallis test. RESULTS: Both MPTP and ZnD diet treatments led to a significant reduction in blood Zn concentrations (PMPTP = 0.012, PZn = 0.014), reduced total distance traveled (PMPTP < 0.001, PZn = 0.031), and affected the degeneration of dopaminergic neurons in the substantia nigra (PMPTP < 0.001, PZn = 0.020). In the MPTP-treated mice, the ZnD diet significantly reduced total distance traveled by 22.4% (P = 0.026), decreased latency to fall by 49.9% (P = 0.026), and reduced dopaminergic neurons by 59.3% (P = 0.002) compared with the ZnA diet. RNA sequencing analysis revealed a total of 301 differentially expressed genes (156 upregulated; 145 downregulated) in the substantia nigra of ZnD mice compared with ZnA mice. The genes were involved in a number of processes, including protein degradation, mitochondria integrity, and α-synuclein aggregation. CONCLUSIONS: Zn deficiency aggravates movement disorders in PD mice. Our results support previous clinical observations and suggest that appropriate Zn supplementation may be beneficial for PD.

Munronin V with 7/7/6 tricarbocyclic framework from Munronia henryi harms inhibits tau pathology by activating autophagy.

Munronin V (1), isolated from Munronia henryi Harms, is the first example, to the best of our knowledge, of an unprecedented 7/7/6 tricarbocyclic framework featuring an unusual A,B-seco-limonoid ring. The structures of munronin V were established from extensive spectroscopic and electronic circular dichroism (ECD) analyses. The novel A,B-seco with two seven-membered lactones was formed as a result of Baeyer-Villiger oxidation. Compound 1 activated autophagy and inhibited Tau pathology as revealed by flow cytometric analyses, confocal imaging analysis and western blotting, and this effect was mediated by transcription factor EB (TFEB). These findings suggested that 1 might have potential as a compound for combating Alzheimer's disease.

Anti-TMV effects of seco-pregnane C21 steroidal glycosides isolated from the roots of Cynanchum paniculatum.

Tobacco mosaic virus (TMV) is known to infect a wide range of plants, resulting in reduced yield and productivity. Novel, effective, and plant-based pesticides are required to protect plants against TMV infection. To identify novel anti-TMV agents from natural sources, we systematically studied the roots of Cynanchum paniculatum and isolated six new seco-pregnane C21 steroidal glycosides, along with 14 known compounds. Their structures were elucidated by comprehensive spectroscopic data analysis. The anti-TMV activity of compounds were screened using the half-leaf method. Biological tests revealed that compounds 1, 2, 5, 9, 10, 15, and 16 displayed significant anti-TMV activities compared with the positive control ningnanmycin. In addition, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis confirmed the antiviral activity of these compounds, as evident from reduced TMV coat protein (TMV-CP) gene replication and TMV-CP protein expression. These compounds downregulated the expression of NtHsp70-1 and NtHsp70-261, indicating that these steroidal glycosides possibly inhibit the TMV infection by suppressing the expression of NtHsp70-1 and NtHsp70-061 expression.

Alantolactone ameliorates cancer cachexia-associated muscle atrophy mainly by inhibiting the STAT3 signaling pathway.

BACKGROUND: Cancer cachexia is a serious metabolic disorder syndrome that is responsible for the deaths of approximately 30% of patients with cancer, but effective drugs for cancer cachexia are still lacking. Inflammatory cytokines such as TNF-α or IL-6 are involved in the induction of skeletal muscle atrophy and fat depletion in patients with cancer cachexia. PURPOSE: In this study, we assessed the therapeutic effects of the natural compound alantolactone (AL) on cancer cachexia and tried to clarify the mechanisms by which it ameliorates muscle atrophy. METHODS: The C26 tumor-bearing cancer cachexia mouse model was used to evaluate the efficacy of AL in alleviating cancer cachexia in vivo. The levels of IL-6 or TNF-α in mouse serum were detected using ELISA kits. Cultured C2C12 myotubes and 3T3-L1 adipocytes treated with conditioned medium of C26 tumor cells, IL-6 or TNF-α were employed as in vitro cancer cachexia models to examine the effects of AL in vitro. RESULTS: AL (5 or 10 mg/kg, qd, i.p.) protected mice with C26 tumors and cachexia from a loss of body weight and muscle wasting but only slightly ameliorated fat loss. The circulating level of IL-6 but not TNF-α was significantly decreased by AL. AL treatment significantly inhibited STAT3 activation in the gastrocnemius (GAS) muscle of cancer cachexia mice. AL (0.125, 0.25, 0.5 and 1 µM) dose-dependently ameliorated myotube atrophy and STAT3 activation in cultured C2C12 myotubes induced by conditioned medium from C26 tumor cells. AL also ameliorated C2C12 myotube atrophy induced by IL-6 and inhibited IL-6-mediated STAT3 activation. AL exhibited weak effects on ameliorating TNF-α-mediated myotube atrophy and NF-κB activation. Only AL at high doses of more than 5 µM ameliorated lipolysis and STAT3 activation induced in mature 3T3-L1 adipocytes by conditioned medium from C26 tumor cells. CONCLUSIONS: AL significantly ameliorated muscle atrophy in a cancer cachexia model mainly through the inhibition of the STAT3 pathway. AL might be a promising lead compound in the development of drug candidates for cancer cachexia therapy.

Comparison of the Distinct, Host-Specific Response of Three Solanaceae Hosts Induced by Phytophthora infestans.

Three Solanaceae hosts (TSHs), S. tuberosum, N. benthamiana and S. lycopersicum, represent the three major phylogenetic clades of Solanaceae plants infected by Phytophthora infestans, which causes late blight, one of the most devastating diseases seriously affecting crop production. However, details regarding how different Solanaceae hosts respond to P. infestans are lacking. Here, we conducted RNA-seq to analyze the transcriptomic data from the TSHs at 12 and 24 h post P. infestans inoculation to capture early expression effects. Macroscopic and microscopic observations showed faster infection processes in S. tuberosum than in N. benthamiana and S. lycopersicum under the same conditions. Analysis of the number of genes and their level of expression indicated that distinct response models were adopted by the TSHs in response to P. infestans. The host-specific infection process led to overlapping but distinct in GO terms and KEGG pathways enriched for differentially expressed genes; many were tightly linked to the immune response in the TSHs. S. tuberosum showed the fastest response and strongest accumulation of reactive oxygen species compared with N. benthamiana and S. lycopersicum, which also had similarities and differences in hormone regulation. Collectively, our study provides an important reference for a better understanding of late blight response mechanisms of different Solanaceae host interactions.

Curcumin ameliorates lipid metabolic disorder and cognitive dysfunction via the ABCA1 transmembrane transport system in APP/PS1 double transgenic mice.

The disorder of lipid metabolism, especially cholesterol metabolism, can promote Alzheimer's Disease. Curcumin can ameliorate lipid metabolic disorder in the brain of Alzheimer's Disease patients, while the mechanism is not clear. APP/PS1 (APPswe/PSEN1dE9) double transgenic mice were divided into dementia, low-dose, and high-dose groups and then fed for six months with different dietary concentrations of curcumin. Morris water maze was used to evaluate the transgenic mice's special cognitive and memory ability in each group. In contrast, the cholesterol oxidase-colorimetric method was used to measure total serum cholesterol and high-density lipoprotein levels. Immunohistochemistry was used to evaluate the expression of liver X receptor-ß, ATP binding cassette A1 and apolipoprotein A1 of the hippocampus and Aß42 in the brains of transgenic mice. The mRNA and protein expression levels of liver X receptor-ß, retinoid X receptor-α and ATP binding cassette A1 were evaluated using qRT-PCR and Western blotting, respectively. Curcumin improved the special cognitive and memory ability of transgenic Alzheimer's Disease Mice. The total serum cholesterol decreased in Alzheimer's Disease mice fed the curcumin diet, while the high-density lipoprotein increased. The curcumin diet was associated with reduced expression of Aß and increased expression of liver X receptor-ß, ATP binding cassette A1, and apolipoprotein A1 in the CA1 region of the hippocampus. The mRNA and protein levels of retinoid X receptor-α, liver X receptor-ß, and ATP binding cassette A1 were higher in the brains of Alzheimer's Disease mice fed the curcumin diet. Our results point to the mechanism by which curcumin improves lipid metabolic disorders in Alzheimer's Disease via the ATP binding cassette A1 transmembrane transport system.

Plastic film mulching affects N2O emission and ammonia oxidizers in drip irrigated potato soil in northwest China.

In soil, ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) are regarded as key factors mediating nitrous oxide (N2O) production and emission. However, there are scarce reports about the effect of film mulching on ammonia oxidizers, and the biological nitrification process of N2O emission is unclear. This study was based on potato field experiments under different mulching films, including polyethylene mulching film (PM), transparent degradable mulching film (TDM), black degradable mulching film (BDM), and bare land (CK). AOB and AOA abundances were estimated using real-time PCR, and their diversity and community structure were measured using high-throughput sequencing. Result revealed that the total N2O emission from CK was 12.32%-41.03% higher than that from film mulching soil. Under film mulching, according to total N2O emission from soil and N2O concentration in soil treatments were ordered as PM > BDM > TDM, and N2O production was closely correlated with copy numbers of the amoA gene. BDM significantly increased the number of amoA-AOB gene copies (P < 0.01), and PM significantly increased the those of amoA-AOA (P < 0.01). BDM and TDM increased AOB operational taxonomic units (OTUs), Chao1, Simpson, and Shannon indices, while PM increased the AOA OTUs and Chao1 index. Variations in AOA abundance and diversity were closely related to soil mineral N and temperature changes induced by polyethylene film mulching (P < 0.05), whereas AOB showed no significant association with soil properties. Meanwhile, we did not find a distinct treatment effect on AOB community structure. Our findings indicate that (i) degradable film mulching increased AOB abundance and diversity and N2O concentration, but obviously reduced N2O emissions, and (ii) AOA were more sensitive than AOB to polyethylene mulching film.

Efficient Synthesis of Cannabigerol, Grifolin, and Piperogalin via Alumina-Promoted Allylation.

The synthesis of three phenolic natural products has been accomplished with unprecedented efficiency using a new alumina-promoted regioselective aromatic allylation reaction. Cannabigerol and grifolin were prepared in one step from the inexpensive 5-alkyl-resorcinols olivetol and orcinol. Piperogalin was synthesized, for the first time, via two sequential allylations of orcinol with geraniol and prenol.

Organic manure input improves soil water and nutrients use for sustainable maize (Zea mays. L) productivity on the Loess Plateau.

Long-term chemical fertilizer input causes soil organic matter losses, structural compaction, and changes in soil water and nutrient availability, which have been subdued in the most of dry farmland in China. The concept of "more efficiency with less fertilizer input" has been proposed and is urgently needed in current agriculture. Application of chemical fertilizer combined with organic manure (OM) could be a solution for soil protection and sustainable production of dry-land maize (Zea mays. L). Field research over three consecutive years on the Loess Plateau of China was conducted to evaluate the integrated effects of chemical fertilizer strategies and additional OM input on soil nutrients availability and water use in maize. The results showed that, after harvest, soil bulk density decreased significantly with OM application, concomitant with 11.9, 18.7 and 97.8% increases in topsoil total nitrogen, organic matter, and available phosphorus contents, respectively, compared with those under equal chemical NPK input. Water use in the 1.0-1.5 m soil profile was improved, therefore, the soil conditions were better for maize root growth, leaf area and shoot biomass of individual maize plants increased significantly with OM application. Optimized NPK strategies increased grain yield and water use efficiency by 18.5 and 20.6%, respectively, compared to only chemical NP input. Furthermore, additional OM input promoted yield and water use efficiency by 8.9 and 5.8%, respectively. Addition of OM promotes sustainable soil and maize grain productivity as well as friendly soil environmental management of dry land farming.

[Inner-heating acupuncture of lumbar degenerative lesions based on ß-catenin signaling pathway].

OBJECTIVE: By observing the effect of inner-heating acupuncture on the expression of Wnt1, Axin and ß-catenin in the intervertebral disc of rats with lumbar degenerative disease and to explore the regulatory mechanism of inner-heating acupuncture on the apoptosis of annulus fibrosus cells in rats with lumbar degenerative disease. METHODS: Forty SD rats were randomly divided into normal group, model group, inner heating acupuncture group and acupuncture group with 10 rats in each group. Except for normal group, all rats were modeled. Bilateral Da Chang Shu were selected for inner-heating acupuncture and acupuncture treatment. Western-bolt assay was used to detect the expression of Wnt1, Axin and ß-catenin in rat intervertebral discs. RESULTS: Compared with the model group, Wnt1 and ß-catenin expression in annulus fibrosus cells of rats in the inner heating acupuncture group and the acupuncture group were significantly decreased(P<0.05);the expression of Axin in annulus fibrosus of rats in the inner heating acupuncture group was significantly increased(P<0.05). There was no significant difference in the expression of Axin in annulus fibrosus of rats between acupuncture group and model group(P>0.05). CONCLUSION: Inner heating acupuncture can down regulate the expression of Wnt1 and ß-catenin and up regulate the expression of Axin in annulus fibrosus of rats with lumbar degenerative desease. It is suggested that the mechanism may be to regulate the expression of related factors in the ß-catenin signaling pathway, so as to achieve the goal of treating lumbar degenerative diseases.

Uncovering the Hidden Antibiotic Potential of Cannabis.

The spread of antimicrobial resistance continues to be a priority health concern worldwide, necessitating the exploration of alternative therapies. Cannabis sativa has long been known to contain antibacterial cannabinoids, but their potential to address antibiotic resistance has only been superficially investigated. Here, we show that cannabinoids exhibit antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), inhibit its ability to form biofilms, and eradicate preformed biofilms and stationary phase cells persistent to antibiotics. We show that the mechanism of action of cannabigerol is through targeting the cytoplasmic membrane of Gram-positive bacteria and demonstrate in vivo efficacy of cannabigerol in a murine systemic infection model caused by MRSA. We also show that cannabinoids are effective against Gram-negative organisms whose outer membrane is permeabilized, where cannabigerol acts on the inner membrane. Finally, we demonstrate that cannabinoids work in combination with polymyxin B against multidrug resistant Gram-negative pathogens, revealing the broad-spectrum therapeutic potential for cannabinoids.

Establishment of a mouse model of cancer cachexia with spleen deficiency syndrome and the effects of atractylenolide I.

Cancer cachexia is a multifactorial metabolic syndrome that affects ∼50%-80% of cancer patients, and no effective therapy for cancer cachexia is presently available. In traditional Chinese medicine, a large portion of patients with cancer cachexia was diagnosed as spleen deficiency syndrome and treated with tonifying TCMs that produce clinic benefits. In this study we established a new animal model of spleen deficiency and cancer cachexia in mice and evaluated the therapeutic effects of atractylenolide I, an active component of tonifying TCM BaiZhu, in the mouse model. Cancer cachexia was induced in male BALB/c mice by inoculation of mouse C26 colon adenocarcinoma cells, whereas spleen deficiency syndrome was induced by treating the mice with spleen deficiency-inducing factors, including limited feeding, fatigue, and purging. The mouse model was characterized by both cachexia and spleen deficiency characteristics, including significant body weight loss, cancer growth, muscle atrophy, fat lipolysis, spleen, and thymus atrophy as compared with healthy control mice, cancer cachexia mice, and spleen deficiency mice. Oral administration of atractylenolide I (20 mg· kg-1per day, for 30 days) significantly ameliorated the reduction in body weight and atrophy of muscle, fat, spleen, and thymus in mice with spleen deficiency and cachexia. The established model of spleen deficiency and cancer cachexia might be useful in the future for screening possible anticachexia TCMs and clarifying their mechanisms.

Effect of phosphorus-modified biochars on immobilization of Cu (II), Cd (II), and As (V) in paddy soil.

Novel phosphorus-modified biochars were produced by pyrolyzing biomass feedstocks (wood, bamboo, cornstalk and rice husk) pre-impregnated with potassium phosphate (K3PO4). The soil heavy metal immobilization performance and mechanisms of modified biochars were investigated. Incubation experiments showed that impregnation with phosphorous can decrease the extraction of Cu (II) and Cd (II) by 2 to 3 times. Phosphorus-modified biochars enhanced the transformation of Cu (II) and Cd (II) ions from acid soluble to more stable forms. Characterization results showed that phosphorus (P) compounds in modified biochar played a vital role to immobilize Cu (II) and Cd (II) by forming precipitates or complexes with them. Additionally, the modified rice husk and cornstalk biochars have in the average 14-24% and 19-33% higher immobilization efficiency for Cd (II) and Cu (II) than the other two P-assisted biochars. However, regardless of the feedstock, both the extraction and mobility of As (V) were increased by phosphorous. This study indicates that the P-modified biochar can serve as a novel remediation agent for heavy metal polluted soils.

Prioritized brain selenium retention and selenoprotein expression: Nutritional insights into Parkinson's disease.

Selenium (Se), an essential trace mineral, confers its physiological functions mainly through selenoproteins, most of which are oxidoreductases. Results from animal, epidemiological, and human genetic studies link Parkinson's disease to Se and certain selenoproteins. Parkinson's disease is characterized by multiple motor and non-motor symptoms that are difficult to diagnose at early stages of the pathogenesis. While irreversible, degenerative and age-related, the onset of Parkinson's disease may be delayed through proper dietary and environmental controls. One particular attribute of Se biology is that brain has the highest priority to receive and retain this nutrient even in Se deficiency. Thus, brain Se deficiency is rare; however, a strong body of recent evidence implicates selenoprotein dysfunction in Parkinson's disease. Direct and indirect evidence from mouse models implicate selenoprotein T, glutathione peroxidase 1, selenoprotein P and glutathione peroxidase 4 in counteracting Parkinson's disease through Se transportation to the brain and reduced oxidative stress. It is of future interest to further characterize the full selenoproteomes in various types of brain cells and elucidate the mechanism of their actions in Parkinson's disease.

In vitro and in vivo Study on Glioma Treatment Enhancement by Combining Temozolomide with Calycosin and Formononetin.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalina alpestris is a traditional Chinese herbal medicine with anti-inflammatory, anti-immune, anti-tumor and other pharmacological effects. Calycosin and formononetin (FMN) are two natural compounds isolated from astragalus. It has been shown that calycosin and FMN are active anti-tumor ingredient. AIM OF THE STUDY: The aim of this current work was to study the therapeutic enhancement of temozolomide (TMZ) on gliomavia combining with calycosin and FMN. MATERIALS AND METHODS: The effect of co-administration via hematoxylin-eosin staining (HE staining) was determined by measuring cell proliferation toxicity with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) assay and sequentially observing the cell morphology. To synchronously explore the effect of migration on C6, transwell assay and wound healing assay were performed. Apoptosis was measured by Annexin V/propidium iodide (PI) staining. Meanwhile, western blot was used to investigate proteins involved in the mechanisms for migration and apoptosis. Furthermore, HE staining and immunohistochemistry were also analyzed for curative effect in vivo. RESULTS: The efficacy of TMZ on glioma could be enhanced by combining with calycosin and FMN through inhibiting the proliferation and migration of glioma cells and promoting their apoptosis. Western blot assays indicated that expression of apoptotic proteins (Bcl-2 Associated XProtein (Bax), Cleaved Caspase-3, Cleaved Caspase-9) were up-regulated. Anti-apoptotic protein (B-cell lymphoma-2,Bcl-2) was down-regulated. The migratory proteins (Matrix metallopeptidase 2, 9, MMP-2, MMP-9) was downregulated. In vivo study, this kind of co-administration (calycosin, FMN, and TMZ) exhibited the marked therapeutic effect on glioma. CONCLUSIONS: This study has identified that calycosin and FMN can increase the treatment effect of TMZ in vitro and in vivo. These attractive features substantially broadened the application range of TMZ as a glioma treatment medicine.