Genetic variation features of neonatal hyperbilirubinemia caused by inherited diseases

BACKGROUND Genetic factors play an important role in neonatal hyperbilirubinemia(NH)caused by genetic diseases.AIM To explore the characteristics of genetic mutations associated with NH and analyze the correlation with genetic diseases.METHODS This was a retrospective cohort study.One hundred and five newborn patients diagnosed with NH caused by genetic diseases were enrolled in this study between September 2020 and June 2023 at the Second Affiliated Hospital of Xiamen Medical College.A 24-gene panel was used for gene sequencing to analyze gene mutations in patients.The data were analyzed via Statistical Package for the Social Sciences 20.0 software.RESULTS Seventeen frequently mutated genes were found in the 105 patients.Uridine 5'-diphospho-glucuronosyltransferase 1A1(UGT1A1)variants were identified among the 68 cases of neonatal Gilbert syndrome.In patients with sodium taurocholate cotransporting polypeptide deficiency,the primary mutation identified was Na+/taurocholate cotransporting polypeptide Ntcp(SLC10A1).Adenosine triphosphatase 7B(ATP7B)mutations primarily occur in patients with hepatolenticular degeneration(Wilson's disease).In addition,we found that UGT1A1 and glucose-6-phosphate dehydrogenase mutations were more common in the high-risk group than in the low-risk group,whereas mutations in SLC10A1,ATP7B,and heterozygous 851del4 mutation were more common in the low-risk group.CONCLUSION Genetic mutations are associated with NH and significantly increase the risk of disease in affected newborns.

Structural characterizations andα-glucosidase inhibitory activities of four Lepidium meyenii polysaccharides with different molecular weights

Four polysaccharides(MCPa,MCPb,MCPc,MCPd)were obtained from Lepidium meyenii Walp.Their structures were characterized by chemical and instrumental methods including total sugar,uronic acid and protein content determi-nation,UV,IR and NMR spectroscopy,as well as monosaccharide composition determination and methylation analy-ses.Four polysaccharides were a group of glucans with different molecular weights ranging from 3.12 to 14.4 kDa,and shared a similar backbone chain consisting of(1→4)-glucose linkages with branches attached to C-3 and C-6.Furthermore,bioactivity assay showed that MCPs had concentration-dependent inhibitory activity onα-glucosidase.MCPb(Mw=10.1 kDa)and MCPc(Mw=5.62 kDa)with moderate molecular weights exhibited higher inhibitory activ-ity compared with MCPa and MCPd.

Four undescribed pyrethrins from seeds of Pyrethrum cinerariifolium and their aphidicidal activity

Four undescribed pyrethrins C-F(1-4)as well as four known pyrethrins(5-8)were isolated from seeds of Pyrethrum cinerariifolium Trev.The structures of compounds 1-4 were elucidated by UV,HRESIMS,and NMR(^(1)H and ^(13)C NMR,^(1)H-^(1)H COSY,HSQC,HMBC and ROESY),among which the stereostructure of compound 4 was determined by calcu-lated ECD.Furthermore,compounds 1-4 were evaluated for their aphidicidal activities.The insecticidal assay results showed that 1-4 exhibited moderate aphidicidal activities at the concentration of 0.1 mg/mL with the 24 h mortality rates ranging from 10.58 to 52.98%.Among them,pyrethrin D(2)showed the highest aphidicidal activity,with the 24 h mortality rate of 52.98%,which was slightly lower than the positive control(pyrethrin II,83.52%).

The Lifespan-Promoting Effect of Otophylloside B in Caenorhabditis elegans

Aging is the major risk factor for many human diseases and degeneration.Thus,clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted.In traditional Chinese medicine(TCM),some were claimed to slow down aging.Qingyangshen(Cynanchum otophyllum schneid)is such a TCM.Here,we assayed the longevity effect of compound Otophylloside B(Ot B),a C-21 steroidal glycoside isolated from Qingyangshen,in Caenorhabditis elegans,which is a popular model for aging research.Our results showed that Ot B could modestly extend the lifespan of C.elegans,delay the age-related decline of body movement and improve the stress resistance.Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16.Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor(daf-2).In addition,Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis,for lifespan extension.

Cucurbitane triterpenoids from Hemsleya penxianensis

Two new cucurbitacins,jinfushanencins A(1)and B(2),seven new cucurbitane glycosides,jinfushanosides E-K(3-9),along with nine known analogues,were obtained from the tubers of Hemsleya penxianensis.Their structures were elucidated on the basis of extensive spectroscopic and chemical methods.Selected isolates were tested their anti-HIV-1 activities,and compound 5 showed weak anti-HIV-1 in C8166 cell(EC50=5.9μg/mL)with a selectivity index of 13.5.

Biflavone Ginkgetin,a Novel Wnt Inhibitor,Suppresses the Growth of Medulloblastoma

Medulloblastoma(MB)is a form of malignant brain tumor that predominantly arises in infants and children,of which approximately 25%is due to upregulation of canonical Wnt pathway with mainly mutations in CTNNB1.Therefore,Wnt inhibitors could offer rational therapeutic strategies and chemoprevention for this malignant cancer.In our present study,we undertook a screening for antagonists of Wnt signaling from 600 natural compounds,and identified Ginkgetin,a biflavone isolated from Cephalotaxus fortunei var.alpina.Ginkgetin inhibited Wnt pathway with an IC50 value around 5.92 lM and structure–activity relationship analysis suggested the methoxy group in Ginkgetin as a functional group.Biflavone Ginkgetin showed obvious cytotoxicity in Daoy and D283 MB cells.Cell cycle analysis by flow cytometry showed that Ginkgetin induced efficiently G2/M phase arrest in Daoy cells.Further mechanism studies showed that Ginkgetin reduced the expression of Wnt target genes,including Axin2,cyclinD1 and survivin in MB cells.The phosphorylation level of b-catenin also decreased in a time-and concentration-dependent manner.Collectively,our data suggest that Ginkgetin is a novel inhibitor of Wnt signaling,and as such warrants further exploration as a promising antimedulloblastoma candidate.

New alkaloids from the fruiting bodies of Ganoderma sinense

Four new alkaloids,sinensines B-E(1-4),together with one known alkaloid,sinensine(5),were isolated from the fruiting bodies of Ganoderma sinense.Their structures were elucidated on the basis of 1D and 2D NMR spectra analysis.The structure of sinensine E was confirmed by X-ray crystallographic analysis of its acetyl product(4a).

Six New 9,19-Cycloartane Triterpenoids from Cimicifuga foetida L.

Six new 9,19-cycloartane triterpene derivatives,as well as 3 known analogues(7–9),were isolated from the roots of Cimicifuga foetida L.Their structures were established on the basis of extensive spectroscopic analyses(IR,UV,ORD,HRESIMS,1D and 2D NMR).

Otophylloside B Protects Against AβToxicity in Caenorhabditis elegans Models of Alzheimer’s Disease

Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy,and otophylloside B(Ot B),isolated from C.otophyllum,is the essential active component.Having previously identified anti-aging effects of Ot B,we evaluated Ot B for AD prevention in C.elegant models of AD and found that Ot B extended lifespan,increased heat stress-resistance,delayed body paralysis,and increased the chemotaxis response.Collectively,these results indicated thatOt B protects against Aβtoxicity.Further mechanistic studies revealed that Ot B decreased Aβdeposition by decreasing the expression of Aβat the mRNA level.Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor(HSF)by upregulating the expression of hsf-1 and its target genes,hsp-12.6,hsp-16.2 and hsp-70.Ot B also increased the expression of sod-3 by partially activating DAF-16,while SKN-1 was not essential in Ot B-mediated protection against Aβtoxicity.

Cycloartane Glycosides from the Roots of Cimicifuga foetida with Wnt Signaling Pathway Inhibitory Activity

Four new 9,19-cycloartane triterpenoids,cimilactone E(1),cimilactone F(2),20-O-(E)-butenoyl-23-epi-26-deoxyactein(3),and 20,12b-O-diacetylcimiracemonol-3-O-b-D-xylopyranoside(4),together with four known constituents(5–8)were isolated from the roots of Cimicifuga foetida.The new structures were elucidated by extensive spectroscopic analysis.In addition,compounds 7 and 8 showed significant Wnt signaling pathway inhibitory activity,with IC50 values of 3.33 and 13.34 lM,respectively,using the luciferase reporter gene assay.

Progress on the Chemical Constituents Derived from Glucosinolates in Maca(Lepidium meyenii)

Maca(Lepidium meyenii Walp.),a famous food supplement,has drawn an unprecedented international interest over the last two decades.It was assumed that glucosinolates,macamides,macaenes,and alkaloids are the main bioactive components of Maca before.Recently,a series of novel thiohydantoins which generally exhibit a variety of activities have been isolated from Maca.This review focuses on the progress on the main bioactive components of Maca and their biosynthetic pathway,which indicates that macamides,thiohydantoins,and some alkaloids may originate from glucosinolates.Interestingly,thiohydantoins from Maca are the first type of thiohydantoin derivatives to be found from a natural source and may contribute to some significant effects of Maca.

New Dammarane Triterpenoids,Caffruones A–D,from the Cherries of Coffea arabica

In present study,four new dammarane-type triterpenoids,namely caffruones A–D(1–4),were isolated from the cherries of Coffea arabica.Their structures were elucidated by extensive spectroscopic analysis including 1D,2D NMR(HSQC,HMBC,^(1)H–^(1)H COSY,and ROESY),HRMS and IR spectra.This is the first time that tetracyclic triterpenes have been reported in genus Coffea.

Lactam Triterpenoids from the Bark of Toona sinensis

Three new limonoid-type triterpenoids,namely toonasins A–C(1–3)with a rare lactam E ring,along with six known compounds(4–9)were isolated from the barks of Toona sinensis.The structures of new compounds were elucidated by interpretation of spectroscopic data,and the relative configuration of compound 1 was further characterized by X-ray crystallographic analyses.The isolated compounds were evaluated for their cytotoxic activities against five human tumor cell lines(HL-60,SMMC-7721,A-549,MCF-7 and SW480),and compounds 3 and 5 showed weak cytotoxicities.

Characterization of New Ent-kaurane Diterpenoids of Yunnan Arabica Coffee Beans

Five new ent-kaurane diterpenoids,named mascaroside Ⅲ–Ⅴ(1–3),and 20-nor-cofaryloside Ⅰ–Ⅱ(4–5),together with seven known diterpenoids,were isolated from methanol extracts of the green coffee beans of Yunnan Arabica Coffee.Their chemical structures were elucidated by extensive spectroscopic analyses.Meanwhile,cytotoxicity assay against HL-60,A-549,SMMC-7721,MCF-7 and SW480 cell lines showed that they have not evident inhibition of cytotoxicity.

Three new physalins from Physalis alkekengi var. franchetii

Three new physalin steroids,physalin Ⅲ(1),physalin IV(2),3-O-methylphysalin X(3),together with five known physalins(4-8)were isolated from the 80%EtOH extract of calyces of Physalis alkekengi var.franchetii.The structures of the new compounds were revealed through 1D and 2D NMR and mass spectroscopic studies.

Triterpenoid alkaloid derivatives from Buxus rugulosa

Four new triterpenoid alkaloid derivatives,buxrugulines A-D(1-4),together with four known ones(5-8),were isolated from the leaves and stems of Buxus rugulosa.The structures of compounds 1-4 were elucidated by NMR and MS spectroscopic analysis.All compounds were assayed for their cytotoxicities against HL-60,SMMC-7721,A549,MCF-7,and SW480 cells lines.

New triterpenoids from the kernels of Azadirachta indica

Three new limonoids(1-3)and a new intact triterpenoid(4),along with three known constituents(5-7),were isolated from the dried kernels(after extracting azadirachtin)of Azadirachta indica.The structures of the new compounds 1-benzoyl-3-deacetyl-1-detigloyl salannin(1),7-tigloyl-12-oxo vilasini(2),azadiralactone(3)and azadirahemiacetal(4)were elucidated by means of spectroscopic analysis.The cytotoxities of these isolated constituents were assayed.

Diterpenoids and Limonoids from the Leaves and Twigs of Swietenia mahagoni

Three new compounds,including two diterpenoids,nemoralisins H and I(1 and 2),and a limonoid,2-methoxy khayseneganin E(3),along with four known constituents(4-7),were isolated from the leaves and twigs of Swietenia mahagoni.Their chemical structures were elucidated by means of spectroscopic analysis.The cytotoxities of these isolated constituents were assayed.

Triterpenoids and Sterols from the Leaves and Twigs of Melia azedarach

Two new triterpenoids(1 and 2)and a new sterol(3),together with six known constituents(4–9),were isolated from the leaves and twigs of Melia azedarach.Their chemical structures were elucidated on the basis of spectroscopic analysis.

New jatropholane-type diterpenes from Jatropha curcas cv.Multiflorum CY Yang

Three new jatropholane-type diterpenoids,jatropholones C-E(1-3),along with seven other known compounds,including sikkimenoid B(4),jatrophaldehyde(5),epi-jatrophaldehyde(6),epi-jatrophol(7),jatrophol(8),jatropholone A(9),and jatropholone B(10),were isolated from the roots of a natural cultivar of Jatropha curcas(J.curcas cv.Multiflorum CY Yang).The structural elucidations of 1-3 were accomplished by extensive NMR analysis.Compounds 4,6,and 8 demonstrated inhibition activity against the microorganisms with the MIC values from 0.10 to 0.18 mg/mL.