Fructus choerospondiatis: A comprehensive review of its traditional uses, chemical composition, pharmacological activities, and clinical studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Choerospondiatis is the dried and mature fruit of Choerospondias axillaris (Roxb.) Burtt et Hill. It has been used for a long time in Tibetan and Mongolian medicine, first recorded in the ancient Tibetan medicine book "Medicine Diagnosis of the King of the Moon" in the early 8th century. Fructus Choerospondiatis shows multiple pharmacological activities, especially in treating cardiovascular diseases. AIM OF THIS REVIEW: This paper reviews the progress in research on the botanical characteristics, traditional uses, chemical constituents, pharmacological activity, clinical studies, and quality control of Fructus Choerospondiatis. This review aims to summarize current research and provide a reference for further development and utilization of Fructus Choerospondiatis resources. METHOD: The sources for this review include the Pharmacopeia of the People's Republic of China (2020), theses, and peer-reviewed papers (in both English and Chinese). Theses and papers were downloaded from electronic databases including Web of Science, PubMed, SciFinder, Scholar, Springer, and China National Knowledge Infrastructure.The search terms used were "Choerospondias axillaris", "C. axillaris", "Choerospondias axillaris (Roxb.) Burtt et Hill", "Fructus choerospondiatis", "Guangzao", "Lapsi", and "Lupsi". RESULTS: Fructus Choerospondiatis contains polyphenols, organic acids, amino acids, fatty acids, polysaccharides, and other chemical components. These ingredients contribute to its diverse pharmacological activities such as antioxidant activity, protection against myocardial ischemia-reperfusion injury, anti-myocardial fibrosis, heart rhythm regulation, anti-tumor, liver protection, and immunity enhancement. It also affects the central nervous system, with the ability to repair damaged nerve cells. CONCLUSION: Fructus Choerospondiatis, with its various chemical compositions and pharmacological activities, is a promising medicinal resource. However, it remains under-researched, particularly in pharmacodynamic material basis and quality control. These areas require further exploration by researchers in the future.

Molecular Engineering of NIR-II/IIb Emitting AIEgen for Multimodal Imaging-Guided Photo-Immunotherapy.

In view of the great challenges related to the complexity and heterogeneity of tumors, efficient combination therapy is an ideal strategy for eliminating primary tumors and inhibiting distant tumors. A novel aggregation-induced emission (AIE) phototherapeutic agent called T-TBBTD is developed, which features a donor-acceptor-donor (D-A-D) structure, enhanced twisted molecule conformation, and prolonged second near-infrared window (NIR-II) emission. The multimodal imaging function of the molecule has significance for its treatment time window and excellent photothermal/photodynamic performance for multimode therapy. The precise molecular structure and versatility provide prospects for molecular therapy for anti-tumor applications. Fluorescence imaging in the NIR-II window offers advantages with enhanced spatial resolution, temporal resolution, and penetration depth. The prepared AIE@R837 NPs also have controllable performance for antitumor photo-immunotherapy. Following local photo-irradiation, AIE@R837 NPs generate abundant heat, and 1 O2 directly kills tumor cells, induces immunogenic cell death (ICD) as a photo-therapeutic effect, and releases R837, which enhances the synergistic effect of antigen presentation and contributes to the long-lasting protective antitumor immunity. A bilateral 4T1 tumor model revealed that this photo-immunotherapy can eliminate primary tumors. More importantly, it has a significant inhibitory effect on distant tumor growth. Therefore, this method can provide a new strategy for tumor therapy.

A natural uORF variant confers phosphorus acquisition diversity in soybean.

Phosphorus (P) is an essential element for all organisms. Because P fertilizers are a non-renewable resource and high fixation in soils, sustainable agriculture requires researchers to improve crop P acquisition efficiency. Here, we report a strong association signal at a locus of CPU1 (component of phosphorus uptake 1), from a genome-wide association study of P acquisition efficiency in a soybean core collection grown in the field. A SEC12-like gene, GmPHF1, is identified as the causal gene for CPU1. GmPHF1 facilitates the ER (endoplasmic reticulum) exit of the phosphate transporter, GmPT4, to the plasma membrane of root epidermal cells. A common SNP in an upstream open reading frame (uORF) of GmPHF1, which alters the abundance of GmPHF1 in a tissue-specific manner, contributes to P acquisition diversity in soybean. A natural genetic variation conditions diversity in soybean P acquisition, which can be used to develop P-efficient soybean genotypes.

Clinical and pathological features and risk factors for primary breast cancer patients.

BACKGROUND: Breast cancer is the most common malignancy in women all around the world. According to the latest statistics in 2018, there were more than 2.08 million new breast cancer cases all around the world and more than 620000 deaths; the proportion of breast cancer deaths in women with cancer is 15%. By studying age, clinicopathological characteristics and molecular classification, age at menarche, age at birth, number of births, number of miscarriages, lactation time, surgical history of benign breast lesions, history of gynecological diseases, and other factors, we retrospectively summarized and compared the disease history of patients with primary breast cancer and patients with benign thyroid tumors admitted to our hospital in the past 10 years to explore the clinicopathological characteristics and risk factors for primary breast cancer. AIM: To investigate the clinical and pathological features and risk factors for primary breast cancer treated at our center in order to provide a reference for the prevention and treatment of breast cancer in the Zhuhai-Macao region. METHODS: Through a retrospective case-control study, 149 patients with primary breast cancer diagnosed and treated at Zhuhai Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2013 to March 2020 were included as a case group, and 165 patients with benign breast tumors diagnosed and treated from January 2019 to March 2020 were included as a control group. The data collected included age, age at menarche, age at first birth, number of births, number of miscarriages, lactation time, history of surgery for benign breast lesions, history of familial malignant tumors, history of gynecological diseases, history of thyroid diseases, and the tumor characteristics of the patients in the case group including pathological diagnosis, pathological type, tumor size, lymph node metastasis, distant metastasis, stage, and molecular classification, among others. In the case group, the chi-square test was used to analyze the clinical and pathological features of patients in three age groups (< 40, 40-59, and ≥ 60 years). A multifactor logistic regression analysis was used to analyze correlations between the two groups. RESULTS: Among 149 patients with primary breast cancer, the average age was 48.20 ± 12.06 years, and the proportion of patients at 40-59 years old was the highest, accounting for 61.8% of cases. The molecular type was mainly luminal B type, accounting for 69.2% of cases, and at the time of diagnosis, the tumor stage was mainly stage I/II, accounting for 62.4% of cases. There were no statistically significant differences in the distributions of tumor location, pathological type, tumor size, lymph node metastasis, stage, or molecular classification among the three age groups (< 40, 40-59, and ≥ 60 years) (P ≥ 0.05). The differences in the distribution of distant metastasis among the three age groups (< 40, 40-59, and ≥ 60 years) were statistically significant (P < 0.01). The differences in lactation time, history of familial malignant tumors, history of gynecological diseases, and history of thyroid diseases between the two groups were not statistically significant (P ≥ 0.05). The differences in age at disease diagnosis, age at menarche, and history of surgery for benign breast lesions were statistically significant (P < 0.01). The difference in age at first birth was also statistically significant (P < 0.05). CONCLUSION: The highest incidence of breast cancer in the Zhuhai-Macao region is present among women aged 40-59 years. There is a larger proportion of stage I/II patients, and the luminal B type is the most common molecular subtype. Distant metastasis occurs mainly in the ≥ 60-year-old group at the first diagnosis; increased age, late age at menarche, and late age at first birth may be risk factors for primary breast cancer, and a history of surgery for benign breast lesions may be a protective factor for primary breast cancer.

Methotrexate-based amphiphilic prodrug nanoaggregates for co-administration of multiple therapeutics and synergistic cancer therapy.

The goal of nanomedicine is to seek strategies that are more efficient to address various limitations and challenges faced by conventional medicines, including lack of target specificity, poor bioavailability, premature degradability, and undesired side effects. Self-assembling drug amphiphiles represent a prospective nanomedicine for cancer therapy owing to their favorable route of administration and therapeutic efficiency compared with pristine drug counterparts. In this work, we report a class of self-deliverable prodrug amphiphiles consisting of the hydrophilic drug methotrexate (MTX) and the hydrophobic anticancer drugs camptothecin (CPT) and doxorubicin (DOX) for targeted and combinational chemotherapy. The disulfide bond and hydrazone bond, which are subject to stimuli-triggered bond cleavage, were introduced to link these therapeutic agents and form two prodrug amphiphiles, named as MTX-CPT and MTX-DOX, respectively, which could self-assemble into stable prodrug nanoaggregates (NAs) in aqueous media. MTX molecules in the prodrug NAs facilitated NA uptake into tumor cells with high expression of folic acid receptors (FRs). This systemic study provided clear evidence of the synergistic therapeutic effect by co-administrating dual prodrug NAs on various tumor cells in vitro and a xenograft tumor model in vivo. The obtained prodrug amphiphiles provide an efficient strategy for the design of multifunctional drug delivery systems and elaborate therapeutic nanoplatforms for cancer chemotherapy. STATEMENT OF SIGNIFICANCE: This work presents two kinds of prodrug amphiphiles that are carrier free and integrate targeted drug delivery, stimuli-triggered drug release, synergistic therapy, and theranostic function into a single system. Reduction/acid active prodrug amphiphiles can self-assemble into micellar nanoaggregates (NAs) at a very low critical aggregation concentration. These NAs exhibit superior stability in physiological environment and disassemble in the presence of tumor cells expressing folic acid receptors or the high glutathione or in low pH tumoral endosomal environment. The induced disassembly of prodrug NAs can "switch on" the inherent fluorescence of the internalized camptothecin or doxorubicin for the detection of tumor cells. Compared to a single type of prodrug NA, co-administration of dual prodrug combination can produce an evident synergistic therapeutic effect against various tumor cells in vitro and inhibit xenograft tumor growth in vivo. The methotrexate-based prodrug amphiphiles may provide a potential strategy for developing multifunctional nanoplatforms and delivery of multiple therapeutics in chemotherapy.

Novel Antihypertensive Prodrug from Grape Seed Proanthocyanidin Extract via Acid-Mediated Depolymerization in the Presence of Captopril: Synthesis, Process Optimization, and Metabolism in Rats.

Grape seed extract contains a high content of proanthocyanidins that can be depolymerized into C-4-substituted (epi)catechin derivatives in the presence of nucleophiles. However, the biological and medicinal values of depolymerization products have been rarely investigated. Recently, we developed a novel depolymerization product (-)-epicatechin-4ß- S-captopril methyl ester (ECC) derived from the reaction of grape seed proanthocyanidin extract with captopril in the presence of acidified methanol. A central composite design was employed to select the most appropriate depolymerization temperature and time to obtain the target product ECC with a high yield. A total of 16 metabolites of ECC in rat urine, feces, and plasma were identified using liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The in vivo results suggested that ECC could release captopril methyl ester and epicatechin, followed by the generation of further metabolites captopril and epicatechin sulfate conjugates. Therefore, ECC may be used as a potential prodrug with synergistic or additive hypotensive effects.

Oral delivery of curcumin via porous polymeric nanoparticles for effective ulcerative colitis therapy.

Oral drug delivery has been considered as a promising strategy for ulcerative colitis (UC) therapy. Here, an emulsion solvent evaporation technique was employed to prepare non-porous curcumin (CUR)-loaded polymeric nanoparticles (NPs) and porous CUR-loaded polymeric NPs in the absence or presence of ammonium bicarbonate. The resultant CUR-loaded NPs (non-porous NPs and porous NPs) had a desirable mean particle size of around 260 nm with a narrow size distribution, a uniform pore size distribution, slightly negative-charged surface, high encapsulation efficiency and controlled drug release capacity. In vitro experiments indicated that Raw 264.7 macrophages exhibited time-dependent accumulation profiles of NPs during the initial 2 h of co-incubation. Furthermore, we found that porous NPs inhibited the secretion of the main pro-inflammatory cytokines (TNF-α, IL-6 and IL-12) and the production of reactive oxygen species much more efficiently than non-porous NPs. Most importantly, in vivo studies demonstrated that oral administered porous NPs had a superior therapeutic efficiency in alleviating UC compared with non-porous NPs. The results collectively suggest that porous polymeric NPs can be exploited as efficient oral drug carriers for UC treatment.

Two new bisabolane sesquiterpenoids from Curcuma longa.

Two new bisabolane derivatives were isolated from the rhizome of Curcuma longa L., and their structures were characterized by analyzing spectroscopic data especially 1D- and 2D-NMR spectra. Relative configurations of two compounds were determined by NOESY correlations.

[Study on inhibitory effect of lycium pigment on lipopolysaccharide-induced uveitis in rats and its mechanism].

OBJECTIVE: To investigate the inhibitory effect of lycium pigment on lipopolysaccharide (LPS)-induced uveitis in rats and its mechanism. METHOD: The rat uveitis model was established by 30-day oral administration of lycium pigment (50, 100, 200 mg x kg(-1)) and footpad injection of LPS. Ocular tissues were collected for a histopathological inspection. The protein, nitric oxide and ADMA in aqueous humor, level of inducible nitric oxide synthase (iNOS) in retina, activities of serum total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and content of malondialdehyde (MDA) were determined by using Western blot, ELISA and biochemical methods. RESULT: According to the pathological study, lycium pigment (50, 100, 200 mg x kg(-1)) could notably reduce the inflammatory cell infiltration around corpus ciliare matrix of uveitis rats, and the concentration of protein and nitric oxide, and increased ADMA in aqueous humor. Lycium pigment (100, 200 mg x kg(-1)) could significantly inhibit the expression of iNOS in ocular tissues. In addition, lycium pigment (100, 200 mg x kg(-1)) also decrease the activities of serum T-AOC, SOD, GSH-PX, and the content of lipid peroxide MDA. CONCLUSION: Lycium pigment has the inhibitory effect on LPS-induced uveitis in rats. Its mechanism is related to the regulation of nitric oxide/ADMA pathway and the improvement of oxidation resistance.

[The transformation of betA gene into the pollen plantlets of Populus simonii x P. nigra].

In this study, betA gene was introduced into the pollen plantlets of Populus simonii x P. nigra using Agrobacterium-mediated transformation. The four kanamycine-resistant plants obtained were identified as transgenic plants by PCR detection and the results were all positive. The result of quantitative real-time PCR detection showed that the betA gene was transcribed and expressed in all the transformed plants, but the transcript levels are different. Test of salt-tolerance of the transgenic plants showed that 80%-00% of transgenic plants were rooted while 0 of non-transgenic plants were rooted at 0.55% NaCl stress, and 0 of transgenic plants were rooted at 0.70%-0.80% NaCl stress. The betaine content analysis showed the betaine content of the transgenic plants are obviously higher than that in non-transgenic plants, so transformation betA gene raised the salt tolerance to the transgenic plants.