The Type Strain of Bifidobacterium indicum Scardovi and Trovatelli 1969 (Approved Lists 1980) is ATCC 25912, not DSM 20214, and Rejection to Reclassify Bifidobacterium coryneforme as Bifidobacterium indicum.

In 2018, Nouioui et al. proposed that Bifidobacterium coryneforme was a later synonym of Bifidobacterium indicum on the basis of the digital DNA-DNA hybridization (dDDH) value (85.0%) between B. coryneforme LMG 18911T and B. indicum LMG 11587T. However, in the study of Scardovi et al. (1970), the type strains of B. indicum and B. coryneforme only exhibited 60% DNA-DNA hybridization value. In the present study, the genomes of B. coryneforme CGMCC 1.2279T, B. coryneforme JCM 5819T, B. indicum JCM 1302T, B. indicum CGMCC 1.2275T, B. indicum DSM 20214T, B. indicum LMG 27437T, B. indicum ATCC 25912T, B. indicum KCTC 3230T, B. indicum CCUG 34985T, were sequenced, and the taxonomic relationship between B. coryneforme and B. indicum was re-evaluated. On the basis of the results presented here, (i) ATCC 25912 and DSM 20214 deposited by Vittorio Scardovi are two different strains; (ii) the type strain of B. indicum is ATCC 25912T (= JCM 1302T = LMG 27437T = CGMCC 1.2275T = KCTC 3230T), and not DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587); (iii) B. coryneforme and B. indicum represent two different species of the genus Bifidobacterium; (iv) strain DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587) belongs to B. coryneforme.

Bifidobacterium apis sp. nov., isolated from the gut of honeybee (Apis mellifera).

A novel bifidobacterium (designated F753-1T) was isolated from the gut of honeybee (Apis mellifera). Strain F753-1T was characterized using a polyphasic taxonomic approach. Strain F753-1T was phylogenetically related to the type strains of Bifidobacterium mizhiensis, Bifidobacterium asteroides, Bifidobacterium choladohabitans, Bifidobacterium mellis, Bifidobacterium apousia and Bifidobacterium polysaccharolyticum, having 98.4-99.8 % 16S rRNA gene sequence similarities. The phylogenomic tree indicated that strain F753-1T was most closely related to the type strains of B. mellis and B. choladohabitans. Strain F753-1T had the highest average nucleotide identity (94.1-94.5 %) and digital DNA-DNA hybridization (56.3 %) values with B. mellis Bin7NT. Acid production from amygdalin, d-fructose, gentiobiose, d-mannose, maltose, sucrose and d-xylose, activity of α-galactosidase, pyruvate utilization and hydrolysis of hippurate could differentiate strain F753-1T from B. mellis CCUG 66113T and B. choladohabitans JCM 34586T. Based upon the data obtained in the present study, a novel species, Bifidobacterium apis sp. nov., is proposed, and the type strain is F753-1T (=CCTCC AB 2023227T=JCM 36562T=LMG 33388T).

Chemical constituents of the aerial parts of Mitracarpus hirtus (L.) DC (Rubiaceae).

A phytochemical investigation of the aerial parts of Mitracarpus hirtus afforded thirteen compounds, including a new naphthoquinone di-glycoside (1), three isopentenyl isoflavones (2-4), four flavonoids (5-8), three iridoid glycosides (9 - 11) and two coumarins (12 and 13). Their structures were elucidated based on extensive spectroscopic analyses, chemical methods, and the comparison with the literature. Among them, compound 1 possesses a 2-(3-methylnaphthalen-2-yl)acetic acid core with two glucosyl groups, compounds 2-4 are the first three representatives from the Rubiaceae family, and compounds 9-11 and 13 were isolated from Mitracarpus genus for the first time. Additionally, compounds 2-4 displayed potent antibacterial activities against Helicobacter pylori G27/HP159/JRES00015 (MIC = 4-16 µg/mL) , comparable to metronidazole. To date, wighteone (2) is the most active isoflavone with favourable predicted ADMET properties reported against H. pylori.

Lactiplantibacillus paraxiangfangensis sp. nov., isolated from traditional Chinese pickle.

Three Gram-stain-positive bacterial strains (designated 231-9T, 142-6 and 463-4) were isolated from traditional Chinese pickle, and were characterized using a polyphasic taxonomic approach. Results of 16S rRNA gene sequence analysis indicated that strains 231-9T, 142-6 and 463-4 were phylogenetically related to the type strains of Lactiplantibacillus xiangfangensis, Lactiplantibacillus garii, Lactiplantibacillus carotarum, Lactiplantibacillus plajomi and Lactiplantibacillus modestisalitolerans, having 98.6-99.9 % 16S rRNA gene sequence similarities. Strains 231-9T, 142-6 and 463-4 were most closely related to the type strain of L. xiangfangensis, having 99.9 % 16S rRNA gene, 95.6 % pheS, 99.4 % rpoA and 98.2 % concatenated pheS and rpoA sequence similarities. Relatively low pheS (95.6 %) sequence similarity indicated that strain 231-9T should be further identified. Strain 231-9T shared 99.7-99.9 % average nucleotide identity (ANI) and 98.8-98.9 % digital DNA-DNA hybridization (dDDH) values with strains 142-6 and 463-4, indicating that they belonged to the same species. The ANI and dDDH values between strain 231-9T and L. xiangfangensis LMG 26013T were 92.4-92.9 and 49.6 %, respectively, less than the threshold for species demarcation (95-96% ANI and 70 % dDDH values, respectively), indicating that strains 231-9T, 142-6 and 463-4 represented a novel species within the genus Lactiplantibacillus. Acid production from d-ribose, d-adonitol, d-galactose and lactose, activity of ß-galactosidase and ß-glucosidase, Voges-Proskauer reaction, hydrolysis of hippurate, resistance to 5 µg ml-1 erythromycin, 100 µg ml-1 tetracycline hydrochloride, 50 µg ml-1 bacitracin, 300 µg ml-1 each of gentamicin sulphate, streptomycin sulphate and neomycin sulphate, tolerance to 6 % NaCl could distinguish strains 231-9T, 142-6 and 463-4 from L. xiangfangensis 3.1.1T. Based upon the data of polyphasic characterization obtained in the present study, a novel species, Lactiplantibacillus paraxiangfangensis sp. nov., is proposed and the type strain is 231-9T (=JCM 36258T=CCTCC AB 2023133T).

Lactobacillus juensis sp. nov. and Lactobacillus rizhaonensis sp. nov., isolated from the gut of honeybee (Apis mellifera).

Four lactic acid bacteria, designated F690T, F697, F790T and F769-2, were isolated from the gut of honeybee (Apis mellifera). Results of 16S rRNA gene sequence analysis indicated that strains F690T and F697 were phylogenetically related to the type strains of Lactobacillus kimbladii, Lactobacillus laiwuensis, Lactobacillus kullabergensis and Lactobacillus huangpiensis, having 99.1-99.6 % 16S rRNA gene sequence similarities; and that strains F790T and F769-2 were most closely related to the type strain of Lactobacillus melliventris, having 99.2-99.3 % 16S rRNA gene sequence similarities. The phylogenies based on concatenated pheS, rpoA, gyrB, hsp60, recA, rpoB and tuf sequences and based on whole genome sequences were identical to that based on 16S rRNA gene sequences. Strains F690T and F697 exhibited the highest average nucleotide identity (ANI; 92.1-93.2 %), digital DNA-DNA hybridization (dDDH; 50-50.1 %) and average amino acid identity (AAI; 94.9-95.1 %) values with L. kimbladii Hma2NT. Strains F790T and F769-2 had the highest ANI (93.1-94 %), dDDH (54.4 %) and AAI (94.4-94.7 %) values with L. melliventris Hma8NT. Based upon the data obtained in the present study, two novel species, Lactobacillus juensis sp. nov. and Lactobacillus rizhaonensis sp. nov., are proposed and the type strains are F690T (=JCM 36259T=CCTCC AB 2023131T) and F790T (=JCM 36260T=CCTCC AB 2023132T), respectively.

Application of computer-aided diagnosis to predict malignancy in BI-RADS 3 breast lesions.

Purpose: To evaluate the ability of computer-aided diagnosis (CAD) system (S-Detect) to identify malignancy in ultrasound (US) -detected BI-RADS 3 breast lesions. Materials and methods: 148 patients with 148 breast lesions categorized as BI-RADS 3 were included in the study between January 2021 and September 2022. The malignancy rate, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) were calculated. Results: In this study, 143 breast lesions were found to be benign, and 5 breast lesions were malignant (malignancy rate, 3.4 %, 95 % confidence interval (CI): 0.5-6.3). The malignancy rate rose significantly to 18.2 % (4/22, 95 % CI: 2.1-34.3) in the high-risk group with a "possibly malignant" CAD result (p = 0.017). With a "possibly benign" CAD result, the malignancy rate decreased to 0.8 % (1/126, 95 % CI: 0-2.2) in the low-risk group (p = 0.297). The AUC, sensitivity, specificity, accuracy, PPV, and NPV of the CAD system in BI-RADS 3 breast lesions were 0.837 (95 % CI: 77.7-89.6), 80.0 % (95 % CI: 73.6-86.4), 87.4 % (95 % CI: 82.0-92.7), 87.2 % (95 % CI: 81.8-92.6), 18.2 % (95 % CI: 2.1-34.3) and 99.2 % (95 % CI: 97.8-100.0), respectively. Conclusions: CAD system (S-Detect) enables radiologists to distinguish a high-risk group and a low-risk group among US-detected BI-RADS 3 breast lesions, so that patients in the low-risk group can receive follow-up without anxiety, while those in the high-risk group with a significantly increased malignancy rate should actively receive biopsy to avoid delayed diagnosis of breast cancer.

Acetogenins from the Stem of Uvaria rufa and Their Cytotoxic Activity.

Four new adjacent bis-tetrahydrofuran acetogenins, bullacin C (7), uvarirufin (9), and uvariasolins III (12) and IV (13), along with 11 known acetogenins, were isolated from the stem of Uvaria rufa. Their structures were elucidated based on spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, and MALDI-MS/MS of the lithium adducts. Absolute configurations were assigned using Mosher ester analysis and ECD measurements. Uvarirufin (9) possesses a unique C-39 skeleton among acetogenins. Most tested acetogenins exhibited cytotoxicity against human cancer cell lines (HCT 116, 22Rv1, MDA-MB-435, OVCAR3). Squamocin (8) and uvarirufin (9) were found to be the most potent, with an IC50 value of 1.2 µM for both in HCT 116 colon cancer cells. Additionally, a new application of Dragendorff's reagent is proposed herein for the TLC detection of acetogenins.

Phytochelatin-Mediated Cultivar-Dependent Cd Accumulations of Lactuca sativa and Implication for Cd Pollution-Safe Cultivars Screening.

Cd pollution-safe cultivar (Cd-PSC) is a feasible strategy to minimize Cd contamination in leafy vegetables. The shoot Cd concentrations of 23 Lactuca sativa cultivars under Cd stress ranged from 0.124 to 2.155 mg·kg-1 with a maximum cultivar difference of 8 folds. Typical Cd-PSC C16 (L) and high-Cd-accumulating cultivar C13 (H) were screened to investigate the mechanisms of Cd accumulations in L. sativa through determining Cd concentrations, Cd subcellular distributions, phytochelatin profiles, and phytochelatin biosynthesis-related genes' expressions. Higher Cd distribution in a heat stable fraction in C13 (H) indicated that the high Cd accumulation trait of C13 (H) mainly depended on the Cd-phytochelatin complexes. Root phytochelatin concentrations were significantly elevated in C13 (H) (5.83 folds) than in C16 (L) (2.69 folds) (p < 0.05) under Cd stress. Significantly downregulated expressions of glutathione S-transferase rather than the regulation of phytochelatin synthesis genes in the root of C13 (H) might be responsible for sufficient glutathione supply for phytochelatins synthesis. These findings suggested that phytochelatin elevation in C13 (H) would favor the Cd root to shoot transportation, which provides new insights into the phytochelatin-related cultivar-dependent Cd accumulating characteristic in L. sativa.

Ganciclovir as a potential treatment for glioma: a systematic review and meta-analysis.

BACKGROUND: Glioma is a challenging malignant tumor with a low survival rate and no effective treatment. Recently, ganciclovir, an antiviral drug, combined with gene therapy and its own antiviral ability, has been proposed as a potential treatment for glioma. However, there are differences in the results of various clinical trials. In this study, we conducted a systematic review and meta-analysis to evaluate the efficacy of ganciclovir in treating glioma. METHODS: We searched databases such as PubMed, EMBASE, and Cochrane Library before March 30, 2023. The search terms included glioma, ganciclovir, valganciclovir and treatment. Calculated 1, 2 and 4-year survival rate by risk difference (RD), and overall survival (OS) by odds ratio (OR). RESULTS: Five randomized controlled trials (RCTs) with a total of 606 high-grade glioma patients were included. The results showed that ganciclovir can improve 2-yeaer (RD = 0.179, 95% CI 0.012-0.346, P = 0.036) and 4-year survival rate (RD = 0.185, 95% CI 0.069-0.3, P = 0.002) and OS (OR 2.393, 95% CI 1.212-4.728, P = 0.012) compared with the control group. CONCLUSIONS: This meta-analysis showed that ganciclovir significantly improved the prognosis of glioma patients. Therefore, we suggest that more cases of ganciclovir as a glioma treatment can be conducted, or a large clinical trial can be designed.

Phenylpropanoid-enriched broccoli seedling extract can reduce inflammatory markers and pain behavior.

BACKGROUND: Pain is a worldwide problem requiring an effective, affordable, non-addictive therapy. Using the edible plant broccoli, a growth protocol was developed to induce a concentrated combinatorial of potential anti-inflammatories in seedlings. METHODS: A growth method was utilized to produce a phenylpropanoid-rich broccoli sprout extract, referred to as Original Extract (OE). OE was concentrated and then resuspended for study of the effects on inflammation events. A rabbit disc model of inflammation and degeneration, and, a mouse model of pain behavior were used for in vivo and in vitro tests. To address aspects of mammalian metabolic processing, the OE was treated with the S9 liver microsome fraction derived from mouse, for use in a mouse in vivo study. Analytical chemistry was performed to identify major chemical species. Continuous variables were analyzed with a number of methods including ANOVA, and two-tailed t tests, as appropriate. RESULTS: In a rabbit spine (disc) injury model, inflammatory markers were reduced, and levels of regenerative markers were increased as a result of OE treatment, both in vivo and in vitro. In a mouse pain behavioral model, after treatment with S9 liver microsome fraction, the resultant extract significantly reduced early and late pain behavior in response to a pain stimulus. The OE itself reduced pain behavior in the mouse pain model, but did not achieve the level of significance observed for S9-treated extract. Analytical chemistry undertaken on the extract constituents revealed identities of the chemical species in OE, and how S9 liver microsome fraction treatment altered species identities and proportions. CONCLUSIONS: In vitro and in vivo results indicate that the OE, and S9-treated OE broccoli extracts are worthwhile materials to develop a non-opiate inflammation and pain-reducing treatment.

Elevation of Lentilactobacillus rapi subsp. dabitei Li et al. 2022 to the species level as Lentilactobacillus dabitei sp. nov.

Lentilactobacillus rapi subsp. dabitei was proposed by Li et al. in 2022. The type strains of L. rapi subsp. dabitei and L. rapi subsp. rapi shared 93.1 % average nucleotide identity and 52.8 % digital DNA-DNA hybridization values. Strain IMAU80584T was proposed as a novel subspecies of L. rapi rather than a novel species of the genus Lentilactobacillus on the basis of similar phenotypic characteristics (including growth temperature and pH, tolerance to NaCl and features based on API 50CH and API ZYM). However, the phenotypic investigation performed by Li et al. was insufficient because some physiological and biochemical characteristics recommended by Mattarelli et al. were not included. In the present study, the taxonomic relationship between L. rapi subsp. dabitei and L. rapi subsp. rapi was re-evaluated. Based upon the data obtained in the present study, we propose to elevate L. rapi subsp. dabitei to the species level as Lentilactobacillus dabitei sp. nov. The type strain is IMAU80584T (=GDMCC 1.2566T=JCM 34647T).

Proposal to Reclassify Companilactobacillus futsaii subsp. chongqingensis as a Later Heterotypic Synonym of Companilactobacillus futsaii subsp. futsaii.

Previous studies have shown that Lactobacillus futsaii (now Companilactobacillus futsaii) can be subdivided at the subspecies level. The main purpose of this study is to explore whether this is correct by using a polyphasic taxonomic approach. Lactobacillus futsaii subsp. chongqingii was proposed and effectively published in 2019. The names L. futsaii subsp. chongqingensis corrig. and Lactobacillus futsaii subsp. futsaii were not validated until March 2023. However, in the reclassification of the genus Lactobacillus by Zheng et al. in April 2020, L. futsaii was transferred to Companilactobacillus as Companilactobacillus futsaii. So Lactobacillus futsaii subsp. chongqingensis and Lactobacillus futsaii subsp. futsaii should be transferred to Companilactobacillus futsaii now. In the present study, the relationship between L. futsaii subsp. chongqingensis and L. futsaii subsp. futsaii was re-evaluated. The type strains of L. futsaii subsp. chongqingensis and L. futsaii subsp. futsaii shared identical pheS and rpoA sequences, high dDDH value, similar phenotypic characteristics and fatty acid compositions, indicating that they belonged to the same subspecies. Here, we propose to reclassify Lactobacillus futsaii subsp. chongqingensis and Lactobacillus futsaii subsp. futsaii as Companilactobacillus futsaii subsp. chongqingensis comb. nov. and Companilactobacillus futsaii subsp. futsaii comb. nov., respectively, and Companilactobacillus futsaii subsp. chongqingensis as a later heterotypic synonym of Companilactobacillus futsaii subsp. futsaii.

Clinical Application of Computer-Aided Diagnosis System in Breast Ultrasound: A Prospective Multicenter Study.

OBJECTIVES: Ultrasound tends to present very high sensitivity but relatively low specificity and positive predictive value (PPV), which would result in unnecessary breast biopsies. The purpose of this study is to analyze the diagnostic performance of computer-aided diagnosis (CAD) (S-Detect) system in differentiating breast lesions and reducing unnecessary biopsies in non-university hospitals in less-developed regions of China. METHODS: The study was a prospective multicenter study from 8 hospitals. The ultrasound images, and cine, CAD analysis, and BI-RADS were recorded. The accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the curve (AUC) were analyzed and compared between CAD and radiologists. The Youden Index (YI) was used to determine optimal cut-off for the number of planes to downgrade. RESULTS: A total of 491 breast lesions were included in the study. Less-experienced radiologists combined CAD was superior to less-experienced radiologists alone in AUC (0.878 vs 0.712, p < 0.001), and specificity (81.3% vs 44.6%, p < 0.001). There was no statistical difference in AUC (0.891 vs 0.878, p = 0.346), and specificity (82.3% vs 81.3%, p = 0.791) between experienced radiologists and less-experienced radiologists combined CAD. With CAD assistance, the biopsy rate of less-experienced radiologists was significantly decreased (100.0% vs 25.6%, p < 0.001), and malignant rate of biopsy was significantly increased (15.0% vs 43.9%, p < 0.001). CONCLUSIONS: CAD system can be an effective auxiliary tool in differentiating breast lesions and reducing unnecessary biopsies for radiologists from non-university hospitals in less-developed regions of China.

Role of LncRNA MIR99AHG in breast cancer: Bioinformatic analysis and preliminary verification.

Objective: This research was aimed to preliminarily explore the clinical roles and potential molecular mechanisms of MIR99AHG and its significant transcripts in breast cancer (BRCA). Methods: Public databases were utilized to analyze the expression and prognostic roles of MIR99AHG and its transcripts. Relationships between MIR99AHG expression and immune cells infiltration were analyzed in Xiantao platform. In addition, co-expressed genes and interacting proteins of MIR99AHG were predicted. CancerSEA analyzed its relationship with functional states. Next, CNV status, DNA methylation, interacting transcription factors (TFs) and ceRNA network were analyzed to explore its possible mechanisms. Then, RNA ISH and FISH assays were used to detect its expression and location in BRCA tissues and cell lines, respectively. Finally, qRT-PCR was utilized to investigate MIR99AHG expression in cell lines. Results: Compared with the corresponding normal tissues, MIR99AHG expression levels were lower in all BRCA subtypes, and luminal B's was the lowest one. And MIR99AHG expression was negatively related to the tumor stage. In addition, 4 transcripts (ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5) of MIR99AHG showed significant differences in the expression. Databases also suggested that the high MIR99AHG expression levels indicated good prognosis, especially in patients without lymph node metastasis. Xiantao found that MIR99AHG was positively related to 17 immune cells and negatively linked with 2 immune cells. CancerSEA analysis showed no relationships between MIR99AHG and functional states. From GEPIA and BCIP databases, 19 co-expressed genes were highly related to these four significant transcripts of MIR99AHG. StarBase, RNAct and HDOCK showed that several tumor-associated proteins, including U2AF65, hnRNPC, AEBP2, CHIC1 and so on, might interact with MIR99AHG. Genetically, BRCA had a higher proportion of MIR99AHG CNV loss than CNV gain, and the high level of DNA methylation indicated a good prognosis. Furthermore, 19 TFs were predicted to combine with the promoter of MIR99AHG. Then, we screened out 10 miRNAs potentially interacting with the significant transcripts of MIR99AHG, and five were significantly increased in breast tumors compared to normal tissues, including miR-194-5p, miR-320 b and so on, which could combine 14 mRNAs. Through ISH and FISH assays, we verified that MIR99AHG was down-regulated in BRCA samples and cell lines in comparison to non-tumor tissues and mammary epithelial cell line (MCF10A), and MIR99AHG was located both in cytoplasm and nucleus. qRT-PCR assay also showed the lower expression of MIR99AHG in breast cancer cells than that in MCF10A. Conclusion: These results indicate that MIR99AHG can be a favorable prognostic indicator for BRCA. ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5 are significant transcripts and their down-regulation may play crucial roles in the progression of BRCA.

Polyoxygenated cyclohexene derivatives and other constituents of Uvaria rufa stem.

Six undescribed compounds, uvarirufols D and E, (+)-uvarigranol B, (-)-uvarigranol E, 6-acetoxy-5-hydroxy-7-methoxyflavanone and cherrevenaphthalene D, along with twelve known compounds, including polyoxygenated cyclohexenes, flavonoids, and lignans, were isolated from the methanol extract of Uvaria rufa stems. Their structures were elucidated by spectroscopic analyses and the absolute configurations were determined using electronic circular dichroism. Several isolates were evaluated for cytotoxic, antitubercular and anti-inflammatory potentials. (-)-6-Acetylzeylenol showed moderate inhibitory activity against Mycobacterium tuberculosis, with MIC value of 47.10 µg/mL. Cherrevenaphthalene D exhibited weak antimycobacterial activity and potent inhibitory effect on lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells (EC50 = 8.54 µM). 8-Hydroxy-5,7-dimethoxyflavanone displayed moderate level of NO inhibition (EC50 = 43.62 µM) with little cytotoxicity. The polyoxygenated cyclohexenes and lignans were inactive against HCT 116 and 22Rv1 cancer cells (IC50 > 100 µM).

Association between new plasma inflammatory markers and risk of colorectal neoplasms in individuals over 50 years old.

OBJECTIVE(S): The prognostic value of systemic cytokine profiles and inflammatory markers in colorectal cancer were explored by several studies. We want to know more about inflammatory biomarkers in colorectal adenoma and early cancer. METHOD: The level of 38 inflammatory markers in the plasma of 112 adenoma patients, 72 Tis-T1 staging of colorectal carcinoma patients, 34 T2-T4 staging of colorectal carcinoma patients and 53 normal subjects were detected and compared. RESULT(S): Eight inflammatory biomarkers (Eotaxin, GCSF, IL-4, IL-5, IL-17E, MCP-1, TNF-α and VEGF-A) have higher plasma concentrations in colorectal adenoma and cancer patients compared with normal participants over 50 years old. CONCLUSION(S): Inflammatory markers may have the prognostic value for colorectal adenoma and early-stage carcinoma.

Structurally diverse (9ß-H)-pimarane derivatives with six frameworks from the leaves of Icacina oliviformis and their cytotoxic activities.

Thirteen previously undescribed (9ß-H)-pimarane derivatives, icacinolides A-G (1-7) and oliviformislactones C-H (8-13), together with four known analogs (14-17), were isolated from the leaves of Icacina oliviformis. Their structures were constructed by extensive spectroscopic analysis, 13C NMR-DP4+ analysis, ECD calculation, single-crystal X-ray diffraction, and chemical methods. These structurally diverse isolates were classified into six framework types: rearranged 3-epi-17-nor-(9ß-H)-pimarane, rearranged 17-nor-(9ß-H)-pimarane, 16-nor-(9ß-H)-pimarane, 17-nor-(9ß-H)-pimarane, 17,19-di-nor-(9ß-H)-pimarane, and (9ß-H)-pimarane. Among them, compounds 1, 5, and 7 were the first examples of three rearranged 3-epi-17-nor-(9ß-H)-pimaranes featuring a unique (11S)-carboxyl-9-oxatricyclo[5.3.1.02,7]dodecane motif with contiguous stereogenic centers, whereas their C-3 epimers, compounds 2-4 and 6 were the second examples of four rearranged 17-nor-(9ß-H)-pimaranes. Additionally, compounds 8 and 12/13 represented the second examples of a 16-nor-(9ß-H)-pimarane and two 17,19-di-nor-(9ß-H)-pimaranes, respectively. In cytotoxic bioassay, compound 2 exhibited significant cytotoxic against HT-29 with IC50 values of 7.88 µM, even stronger than 5-fluorouracil, and 15 showed broad-spectrum cytotoxic activities against HepG2, HT-29, and MIA PaCa-2 with IC50 values of 11.62, 9.77, and 4.91 µM, respectively. Meanwhile, a preliminary structure-activity relationship suggested that 3,20-epoxy, 6,19-lactone, 2-OH, 7-OH, and 8-OH in (9ß-H)-pimarane derivatives might be active groups, whereas ring C aromatization may decrease the cytotoxic activities.

Application and Effectiveness of Chinese Medicine in Regulating Immune Checkpoint Pathways.

Immunotherapy targeting immune checkpoint molecules has emerged as a key approach in cancer treatment, representing the forefront of antitumor research. However, studies on immune checkpoint molecules have mainly focused on targeted therapies. Chinese medicine (CM) research as a complementary medicine has revealed that immune checkpoint molecules also undergo disease-specific changes in the context of autoimmune diseases. This review article presents a comprehensive analysis of CM studies on immune checkpoint molecules in the last 5 years, with a focus on their role in different diseases and treatment modalities. CM research predominantly utilizes oral administration of herbal plant extracts or acupuncture techniques, which stimulate the immune system by activating specific acupoints through temperature and needling. In this study, we analyzed the modulation and mechanisms of immune checkpoint molecules associated with different coinhibitory and costimulatory molecules, and reviewed the immune functions of related molecules and CM studies in treating autoimmune diseases and tumors. By summarizing the characteristics and research value of CM in regulating immune checkpoint molecules, this review aims to provide a useful reference for future studies in this field.