The prevalence of Pfk13 polymorphism in malaria patients treated with artemisinin-based therapy: a systematic review and meta-analysis.

Artemisinin (ART) combination therapy is the main treatment for malaria. Pfk13 mutations (or K13 mutations, Kelch 13) are associated with ART resistance. This study aims to conduct a systematic review and meta-analysis of the prevalence of K13 mutations with ART resistance in malaria-endemic countries. An electronic search of studies in 2018 and a manual search in 2020 were performed to identify relevant studies. The risk of bias was assessed using the National Institutes of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies. Data analysis was performed using R 4.1.0. Heterogeneity was estimated using the statistic I2 and Cochran Q test. A total of 170 studies were included in our review. Of these, 55 studies investigated the prevalence of K13 mutations in Southeast Asia. The meta-analysis showed that Southeast Asia had the highest prevalence of K13 mutations, whereas Africa, South America, Oceania, and other Asian countries outside Southeast Asia had a low prevalence of K13 mutations. The C580Y mutation was the most common in Southeast Asia with 35.5% (95%CI: 25.4-46.4%), whereas the dominant mutation in Africa was K189T (22.8%, 95%CI: 7.6-43.2%). This study revealed the emergence of ART resistance associated with K13 mutations in Southeast Asia. The diversity of each type of K13 mutation in other regions was also reported.

Chemical constituents from the leaves of Sindora siamensis var. maritima and their antimicrobial and α-glucosidase inhibitory activities.

Two new glycosides, sindosides A-B (1-2), along with 11 previously identified metabolites (3-13), were isolated from an ethanolic extract of the leaves of Sindora siamensis var. maritima. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (IR, NMR, and HRMS). The absolute configuration of compound 1 was established by experimental and calculated ECD spectra. The antimicrobial results revealed that compound 8 selectively inhibited C. albicans fungal with a MIC value of 64 µg/mL, whereas 11 presented a weak inhibition toward E. faecalis, S. aureus, and B. cereus bacterial strains with the same MIC value of 128 µg/mL. Interestingly, compounds 1, 2, 8, 9, and 11 showed α-glucosidase inhibitory activity with IC50 values ranging from 14.42 ± 0.21 to 30.62 ± 0.18 µM, which were more active than the positive control (acarbose, with an IC50 value of 46.78 ± 1.37 µM). Enzyme kinetic analysis revealed that compounds 1, 2, and 11 behaved as uncompetitive inhibitors with Ki values of 8.60 ± 1.04, 5.16 ± 0.73, and 7.17 ± 0.98 µM, respectively.

Undescribed sesquiterpene-diterpene heterodimers from the fruits of Aphanamixis polystachya selectively modulate inflammatory markers in RAW 264.7 cells.

Aphanapolystachones A-C (1-3), three undescribed sesquiterpene-diterpene heterodimers, were obtained from the fruits of Aphanamixis polystachya. Their structures and absolute configurations were identified by extensive analysis of HR-ESI-MS, NMR, experimental and TD-DFT calculated ECD spectra. The biosynthetic pathway of them was also proposed, which is produced by key intermolecular Diels-Alder [4 + 2]-cycloaddition reaction between a guaiane sesquiterpene and an acyclic diterpene. Compounds 1-3 inhibited NO production in LPS activated RAW 264.7 cells with the IC50 values of 1.7 ± 0.2, 3.0 ± 0.3, 5.3 ± 0.3 µM, respectively, lower than that of the positive control L-NMMA (31.5 ± 2.6 µM). In addition, compounds 1-3 significantly reduced IL-6 secretion at diluted concentration of 0.4 µM.

Acylated flavonoid glycosides from Barringtonia pendula and their inhibition on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.

Six new acylated flavonoid glycosides namely barringosides J - O (1-6) along with tephrokaempferoside and barringoside D were isolated from the branches and leaves of Barringtonia pendula. The structural elucidation was confirmed by extensive analysis of their spectroscopic data including HRQTOFMS, 1D and 2D NMR experiments. Moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells were observed for barringosides M (4) and N (5) with IC50 values of 48.40 ± 3.01 and 56.61 ± 3.87 µM, whereas weak inhibition was found for compounds 1-3, 6, and 7 with IC50 values ranging from 64.91 ± 3.68 to 79.80 ± 3.90 µM.

Dimethylbutyrylated Dibenzocyclooctadiene Lignans from the Fruits of Schisandra cauliflora Inhibit NO Production in LPS-Activated RAW264.7 Cells.

From the fruits of Schisandra cauliflora, five new dimethylbutyrylated dibenzocyclooctadiene lignans, named schisandracaurins A-E, were isolated using separation and chromatographic techniques. Their structures were determined by extensive analyses of HR-ESI-MS, NMR, and ECD spectra. The schisandracaurins A-E potentially inhibited NO production in LPS-activated RAW264.7 cells with their IC50 values from 21.4 to 30.3 µM.

Isoryanodane diterpene derivatives from Barringtonia macrocarpa.

From the MeOH residue of Barringtonia macrocarpa branches and leaves, one new isoryanodane diterpene, barringisol (1), and two new isoryanodane diterpene glucosides, barringisosides A and B (2 and 3), were obtained using various chromatographic isolations. The structural characterization was confirmed by spectroscopic methods including 1D, 2D NMR and HR-ESI-QTOF-MS. This is the first isolation of isoryanodane diterpene derivatives from Barringtonia species. Moreover, the in vitro cytotoxicity of 1-3 on three human cancer cell lines (HepG2, LNCaP and MCF7) was also accessed using SRB assays.

Compound K: A systematic review of its anticancer properties and probable mechanisms.

Panax ginseng is a common natural product, which is well-known to have a wide range of pharmacological activities in cancer. Its metabolite, compound K (CK), has been reported to have anticancer activity. We aimed to systematically review the literature for evidence of anticancer effects of CK. We conducted a systematic search in eight databases. We included all in vitro and in vivo studies investigating the anticancer effects of CK with no restrictions. Quality assessment was applied by ToxRTool. Fifty-four articles were included in our study. The purity of CK in our included studies was at least 95%. The in vitro studies reported that CK had a potential anticancer activity on several cell lines including human lung cancer cell lines (A549, PC-9), nasopharyngeal carcinoma cell line (Hk-1), liver cancer cell line (BEL 7402), and pediatric acute myeloid leukemia cell lines (Kasumi-1, MV4-11). The in vivo studies reported a significant decrease in tumor volume in mice treated with CK. CK is a potential supplementary treatment in cancer chemotherapies. The safety and further clinical trials of CK should be explored for future drug development.

Three new chromanes and one new flavone C-glycoside from Mallotus apelta.

Three new chromanes, malloapeltas J-L (1-3), and one new flavone C-glycoside, malloflavoside (4), together with four known compounds, apigenin 6-C-ß-D-xylopyranosyl-8-C-α-L-arabinopyranoside (5), apigenin 6-C-ß-D-glucopyranosyl-8-C-α-L-arabinopyranoside (6), apigenin 7-O-ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranoside (7), and acantrifoside E (8) were isolated from the methanol extract of the leaves of Mallotus apelta. Their chemical structures were determined using spectroscopic methods, including 1D, 2D NMR, and HR-ESI-MS methods. All the isolated compounds were evaluated their cytotoxic activity against human prostate cancer (PC-3) and human breast cancer (MCF-7) cells, but none of them showed cytotoxicities on both human cancer cell lines.

Constituents of Tinospora sinensis and their nitric oxide inhibitory activities.

One new phenylpropanoid glycoside, tinosinen A (1) and 13 known compounds, tinosinen (2), citrusin B (3), picraquassioside C (4), erythro-guaiacylglycerol-ß-O-4'-coniferyl alcohol (5), erythro-guaiacylglycerol-8-O-4'-(sinapyl alcohol) ether (6), erythro-syringylglycerol-8-O-4'-(sinapyl alcohol) ether (7), seco-isolariciresinol 9-O-D-ß-glucopyranoside (8), tinosposide A (9), pinoresinol-4'-O-ß-D-glucopyranoside (10), syringaresinol-4'-O-ß-D-glucopyranoside (11), pinoresinol (12), syringaresinol (13), and lirioresino-ß-dimethyl ether (14) were isolated from the stems of Tinospora sinensis (Lour.) Merr. Their structures were established by detailed spectroscopic studies and comparisons with those reported in the literature. Compound 13 showed significant inhibitory NO production (IC50 value of 38.53 ± 1.90 µM) in RAW264.7 macrophages, LPS-stimulated. Compounds 3-7, 11, 12, and 14 inhibited NO production with IC50 values ranging from 38.53 to 99.07 µM.

New dibenzocyclooctadiene lignans from Kadsura induta with their anti-inflammatory activity.

Five new dibenzocyclooctadiene lignans, named kadsuindutains A-E (1-5), and three known ones schizanrin F (6), schizanrin O (7), and schisantherin J (8) were isolated from the stems of Kadsura induta. Their structures were determined by analyses of HR-ESI-MS, NMR, and ECD spectra. Compounds 1-5 contain a 2',4'-dioxygenated-2',3'-dimethylbutyryl moiety which is rarely reported for dibenzocyclooctadiene lignans. Molecular docking predicted that compounds 1-8 displayed good binding affinity to the active site of iNOS and TNF-α proteins but unstable binding to the active site of COX-2 protein. Additionally, in vitro experiments showed that compounds 1-8 inhibited NO production in LPS-activated RAW264.7 cells with IC50 values from 10.7 µM to 34.0 µM, compared to the positive control L-NMMA (IC50 = 31.2 µM).

Furostane Saponins from the Seeds of Allium ramosum and Their Lipid Accumulation Inhibitory Activity.

Three new furostane saponins, ramofurosides A-C (1-3), and two known saponins, fistulosaponin B (4) and (25R)-26-O-ß-D-glucopyranosyl-1ß,3ß,26-trihydroxyfurosta-5,20(22)-diene-1-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside (5) were isolated from the methanol extract of Allium ramosum seeds. Their structures were identified based on spectroscopic evidence and comparison with those reported in the literature. All compounds were evaluated for reduction of lipid accumulation in HepG2 cell lines. As a result, compounds 1 and 3 showed a significant reduction in total lipid content by 27.93±3.05 and 27.54±1.68 %, respectively, at a concentration of 100 µM.

Glycoside constituents from Miliusa sinensis leaves and their anti-inflammatory and acetylcholine protective effects.

Repeated column chromatography resulted in the isolation of two new glycosides, miliusides A-B (1 and 7), along with six known metabolites (2-6, and 8) from the leaves of Miliusa sinensis Finet and Gagnep. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (NMR, HRMS), as well as comparison with the previous literature. The biological evaluation of acetylcholinesterase (AChE) inhibitory effects and anti-inflammatory activity by measuring nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophage cells, were also conducted. Among them, compounds 5 and 7 exhibited significant AChE inhibitory activities (IC50 = 53.36 ± 4.20 and 88.50 ± 8.79 µM, respectively), compared with the positive control (Galanthamine, IC50 = 1.65 ± 0.15 µM). Only the MeOH extract showed suppression effects on NO production in LPS-induced RAW264.7 cells (IC50 = 38.18 ± 3.25 µg/mL) comparable to that of the positive control, l-NMMA (IC50 = 2.21 ± 0.56 µg/mL).

Phenolic glycosides from Oroxylum indicum.

Two new phenolic glycosides, oroxylumosides A (1) and B (2), along with four known compounds darendoside A (3), leucosceptoside A (4), acteoside (5) and decaffeoylacteoside (6) were isolated from the stem bark of Oroxylum indicum. Their structures were elucidated by extensive analysis of the 1 D and 2 D NMR as well as HR-ESI-QTOF-MS. In addition, compounds 1 - 4 exhibited inhibitory effects on NO production in LPS-stimulated BV2 microglial cell line with IC50 values of 58.2 ± 2.9, 70.6 ± 3.5, 56.8 ± 2.8 and 61.1 ± 3.1 µM, respectively.

Interventional nephrology and vascular access practice: A perspective from South and Southeast Asia.

South and Southeast Asia is the most populated, heterogeneous part of the world. The Association of Vascular Access and InTerventionAl Renal physicians (AVATAR Foundation), India, gathered trends on epidemiology and Interventional Nephrology (IN) for this region. The countries were divided as upper-middle- and higher-income countries as Group-1 and lower and lower-middle-income countries as Group-2. Forty-three percent and 70% patients in the Group 1 and 2 countries had unplanned hemodialysis (HD) initiation. Among the incident HD patients, the dominant Vascular Access (VA) was non-tunneled central catheter (non-TCC) in 70% of Group 2 and tunneled central catheter (TCC) in 32.5% in Group 1 countries. Arterio-Venous Fistula (AVF) in the incident HD patients was observed in 24.5% and 35% of patients in Group-2 and Group-1, respectively. Eight percent and 68.7% of the prevalent HD patients in Group-2 and Group-1 received HD through an AVF respectively. Nephrologists performing any IN procedure were 90% and 60% in Group-2 and Group 1, respectively. The common procedures performed by nephrologists include renal biopsy (93.3%), peritoneal dialysis (PD) catheter insertion (80%), TCC (66.7%) and non-TCC (100%). Constraints for IN include lack of time (73.3%), lack of back-up (40%), lack of training (73.3%), economic issues (33.3%), medico-legal problems (46.6%), no incentive (20%), other interests (46.6%) and institution not supportive (26%). Routine VA surveillance is performed in 12.5% and 83.3% of Group-2 and Group-1, respectively. To conclude, non-TCC and TCC are the most common vascular access in incident HD patients in Group-2 and Group-1, respectively. Lack of training, back-up support and economic constraints were main constraints for IN growth in Group-2 countries.

Five new seco-labdane-type diterpenoids from Caesalpinia latisiliqua.

Five new seco-labdane-type diterpenoids, caesalatisics A-E (1-5), were isolated from the leaves of Caesalpinia latisiliqua (Cav.) Hattink. Their chemical structures were determined using 1D and 2D NMR, mass spectra, and circular dichroism spectroscopies.

Dammarane-type triterpenoid saponins from the flower buds of Panax pseudoginseng with cytotoxic activity.

Phytochemical investigation of a methanol extract of Panax pseudoginseng flower buds resulted in the isolation of 22 dammarane-type triterpenoid saponins, including three new compounds, pseudoginsenosides A-C (1-3), and 19 known analogs. Their chemical structures were identified by the comprehensive spectroscopic methods, including 1 D and 2 D NMR and mass spectra. In addition, their cytotoxic effects toward three human carcinoma cell lines, including liver (HepG2), breast (MCF7), and lung (A549) were also evaluated.

Sesquiterpenoids from Saussurea costus.

Sixteen sesquiterpenoids (1 - 16), including two new compounds namely saussucostusosides A and B (1 and 2), were isolated from the roots of Saussurea costus by various chromatographic separations. Their structures were elucidated by 1 D and 2 D NMR and HR-QTOF-MS experiments. Among isolated compounds, costunlide (6), 3ß-[4-hydroxymethacryloyloxy]-8α-hydroxycostunolide (10) and 11ß,13-dihydrozaluzanin C (16) exhibited potent inhibitory effects on LPS-induced NO production in RAW264.7 cells with IC50 values of 7.08 ± 0.34, 2.40 ± 0.06 and 5.55 ± 0.24 µM, respectively.

Pregnane glycosides from Gymnema inodorum and their α-glucosidase inhibitory activity.

Two new pregnane glycosides, gyminosides A and B (1 and 2) and three known, tinctoroside B (3), tinctoroside C (4), and gymnepregoside F (5) were isolated from the leaves of Gymnema inodorum (Lour.) Decne. Their structures were elucidated by physical and chemical methods and comparing with those reported in the literature. All these compounds were evaluated for α-glucosidase assay. Compound 5 exhibited the most anti α-glucosidase activity with inhibitory percentage of 63.7 ± 3.9% at the concentration of 200 µM. Compounds 1-4 showed moderate anti α-glucosidase activity with inhibitory percentage ranging from 40.0 to 52.1%.