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Background: Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by scarce adipose tissue. This disease is distributed worldwide, but little is known about these patients in the Chinese population. Here, we delineate the phenotype and prognosis of CGL in our cohort.Methods: Patients diagnosed with CGL from 8 medical centers were reviewed. The initial presentation, laboratory findings, and molecular testing were retrospectively analyzed.Results: A total of 16 patients were analyzed, and the current median age was 3.5 years (range, 9 months-17.5 years). In all patients, molecular results confirmed BSCL2 mutation. c.782dupG (p.Ile262Hisfs*12) was the most common genotype identified. All patients had triangular faces and muscular hypertrophy. In addition, 75% presented with hepatomegaly, 19% had cardiomegaly, and 44% exhibited acanthosis nigricans. Developmental delay was noted in 5 out of 9 patients (56%) with a median developmental quotient (DQ)/intelligence quotient (IQ) of 61. Thirteen patients (81.3%) had high triglyceride levels. Eight patients received leptin analysis, and 7 of them (88%) had low leptin levels. One patient exclusively received a lipid-lowering drug, 4 patients were exclusively placed on a fat-restricted diet, 5 patients were administered combination therapy, and 5 patients received no treatment. Three patients (19%) who developed diabetes mellitus received both oral hypoglycemic agents and insulin. Three patients (19%) experienced loss of ambulation and died prematurely.Conclusion: Our findings highlight the uniqueness of the genotype and phenotype in our cohort. Further long-term surveillance for comorbidities is necessary for early detection and management of these patients. [ABSTRACT FROM AUTHOR]

Background: Hepatobiliary disease currently serves as an urgent health issue in public due to health-modulating factors such as extension of life expectancy, increasingly sedentary lifestyles and over-nutrition. A definite treatment remains lacking owing to different stages of the disease itself and its intricate pathogenesis. Traditional Chinese medicine (TCM) has been gradually popularized in clinic with the satisfactory efficacy and good safety. Curcumae Rhizoma (called E Zhu, EZ in Chinese) is a representative herb, which has been used to treat hepatobiliary disease for thousands of years.Purpose: To systematically summarize the recent research advances on the pharmacological activities of EZ and its constituents, explain the underlying mechanisms of preventing and treating hepatobiliary diseases, and assess the shortcomings of existing work. Besides, ethnopharmacology, phytochemicals, and toxicology of EZ have been researched.Methods: The information about EZ was collected from various sources including classic books about Chinese herbal medicine, and scientific databases including Web of Science, PubMed, ScienceDirect, Springer, ACS, SCOPUS, CNKI, CSTJ, and WANFANG using keywords given below and terms like pharmacological and phytochemical details of this plant.Results: The chemical constituents isolated and identified from EZ, such as terpenoids including β-elemene, furanodiene, germacrone, etc. and curcuminoids including curcumin, demethoxycurcumin, bisdemethoxycurcumin, etc. prove to have hepatoprotective effect, anti-liver fibrotic effect, anti-fatty liver effect, anti-liver neoplastic effect, and cholagogic effect through TGF-β1/Smad, JNK1/2-ROS, NF-κB and other anti-inflammatory and antioxidant signaling pathways. Also, EZ is often combined with other Chinese herbs in the treatment of hepatobiliary diseases with good clinical efficacy and no obvious adverse reactions.Conclusion: It provides a preclinical basis for the efficacy of EZ as an effective therapeutic agent for the prevention and treatment of hepatobiliary diseases. Even so, the further studies still needed to alleviate hepatotoxicity and expand clinical application. [ABSTRACT FROM AUTHOR]

Catechin and epicatechin are the health beneficial flavan-3-ols in tea and many fruits. However, their extreme hydrophilicity renders drawbacks for them to pass through the bio-membranes. We prepared lipophilic flavan-3-ol derivatives by acetylation or by acetone-conjugation. The structures of these derivatives were determined based on their NMR and MS spectra. The 3,5- and 3,7-diacetyl derivatives showed radical scavenging activity slightly weaker than catechin and epicatechin, but showed significantly enhanced capacity to penetrate into living cells. Moreover, the diacetyl derivatives released flavan-3-ols inside cells, while catechin or epicatechin themselves could not penetrate into the cells. The acetone conjugates showed strong antioxidant activity and were able to enter into living cells in the intact form. The acetylated and acetone-conjugated derivatives protected H 2 O 2 -induced erythrocyte hemolysis more effectively than catechin and epicatechin. These results indicated that acetylated and acetone-conjugated flavan-3-ols are promising compounds with less hydrophilicity and better bioactivities in biological systems. [ABSTRACT FROM AUTHOR]

Highlights: [•] Conjugates of flavan-3-ols with cysteine or acetylcysteine were prepared. [•] The preparation was simple, and all of the reagents were edible. [•] The conjugates had greater radical-scavenging activity than the flavan-3-ols. [•] The flavan-3-ol-cysteine conjugates were active against α-glucosidase. [Copyright &y& Elsevier]

Highlights: [•] We compared routines-based early intervention vs. traditional home visiting. [•] We examined changes in progress rates in functional and developmental domains. [•] Between-group differences in progress were seen in selected functional domains. [•] Effects seen for functional outcomes with routines-based early intervention. [•] Sustained post-intervention effect for the routines-based early intervention group. [Copyright &y& Elsevier]

Abstract: The water soluble green tea polyphenol epigallocatechin gallate (EGCG) was lipophilised by esterification with different fatty acids for expanded applications. Four lipophilic ester derivatives of EGCG, namely EGCG-O-tetrastearate, EGCG-O-tetraeicosapentaenoate, EGCG-O-tetradocosahexaenoate, and EGCG-O-octabutyrate, were prepared and evaluated for their antioxidant and antiviral activities in vitro. Incorporation of fatty acids, especially the long chain polyunsaturated fatty acids (PUFA), into EGCG resulted in increased peroxyl radical scavenging activity, as measured by ORAC (oxygen radical absorbance capacity) assay, and metal chelation capacity. However, the esters exhibited decreased reducing power. Antiviral activities of EGCG derivatives were remarkably higher than the parent EGCG molecule, which showed relatively weak effects. The EGCG–PUFA esters were 1700-fold more effective in inhibiting hepatitis C virus (HCV) protease than the positive control embelin. The derivatives also acted as α-glucosidase inhibitors, suggesting their potential in anti-HIV (human immunodeficiency virus) treatment. The results suggest that ester derivatives of EGCG with improved bioactivities may serve as excellent functional food ingredients and natural health products. Moreover, the omega-3 PUFA in the derivatives may also render additional or synergistic health benefits. [Copyright &y& Elsevier]

Abstract: New derivatives of caffeic acid and quinic acid were synthesized and their anti-fungal and inhibitory activities on fungal 1,3-β-glucan synthase were determined in comparison with those of the corresponding chlorogenic acid derivatives. All the chlorogenic, quinic and caffeic acid derivatives that were coupled with an H2N-orn-4-(octyloxy) aniline group (1, 1b and 1c) displayed potent activities in both anti-fungal and inhibition of 1,3-glucan synthase assays. Compounds 1 and 1c inhibited the fungal membrane enzyme with the potency comparable to that of a known 1,3-β-d-glucan synthase inhibitor, aculeacin A. The results revealed that the anti-fungal activity of the chlorogenic acid derivative with a free amino group was at least partly due to inhibition of the fungal 1,3-β-glucan synthase. These results suggest that further investigation on caffeic acid derivatives may lead to the discovery of novel anti-fungal agents with drug-like properties. [ABSTRACT FROM AUTHOR]

Abstract: In our continued research on chlorogenic acid analogues and derivatives with improved bioactivity, we have synthesized some caffeoyl 5,6-anhydroquinic acid derivatives. The 1,7 acetonides of chlorogenic acid (15), and of the mono-caffeoyl 5,6-anhydroquinic acids (7–8) showed appreciable anti-HIV activity. The 3,4-dicaffeoyl 5,6-anhydroquinic acid (12) exhibited an anti-HIV activity twice as that of 3,5-dicaffeoylquinic acid (22). The caffeoyl 5,6-anhydroquinic acid derivatives displayed potent anti-oxidant activities. The mono-caffeoyl 5,6-anhydroquinic acids (10–11) were more than twice stronger than chlorogenic acid (21) on SOD-like activity. [Copyright &y& Elsevier]

Abstract: Flavan-3-ol oligomers from the stems of Cynomorium songaricum were found to show potent SOD-like activity with one of the dimers being most potent. The flavan-3-ols also showed inhibitory activity on α-glucosidase, implying the beneficial effects of this herb on diabetes patients. The total (extractable and non-extractable) tannin content of this herb was found to be as high as 18.3%. The contents of catechin, flavan-3-ol oligomers and extractable tannins using 70% acetone, methanol or water were analysed. It was found that 70% acetone was the most efficient extract solvent amongst these three solvents, especially for higher flavan-3-ol oligomers. [Copyright &y& Elsevier]

Abstract: 2,3-Seco-dioic acids derived from four different triterpene skeletons were prepared and evaluated for their anti-HIV-1 protease activity. Two A-seco derivatives showed potent inhibitory activity against HIV-1 protease (3c and 3e, IC50 5.7 and 3.9μM, respectively), while four other derivatives showed moderate to weak inhibition (3a, 3b, 3d and 3f, IC50 15.7–88.1μM). The combination of a 2,3-seco-2,3-dioic acid functional group in ring A and a free acid group at C-28 or C-30 significantly enhanced HIV-1 protease inhibitory activity (3a, 3c–3e, IC50 3.9–17.6μM). On the other hand, all A-seco derivatives were found to be very weak inhibitors of HCV, renin and trypsin proteases (IC50 >80μM). These findings indicate that A-seco triterpenes with a carboxyl group at C-28 or C-30 are novel and highly selective HIV-1 protease inhibitors. [Copyright &y& Elsevier]

Abstract: Three artificial triterpenoids, (20R)-20,25-epoxy-dammaran-2-en-6α,12β-diol (1), (20R)-20,25-epoxy-3-methyl-28-nordammaran-2-en-6α,12β-diol (2) and isodehydroprotopanaxatriol (3), were isolated from an acidic hydrolysate of Panax ginseng C.A. Meyer, along with three known triterpenes, (20R)-panaxadiol (4), (20R)-panaxatriol (5) and oleanolic acid (6). Compounds 1–3 and 6 showed inhibitory activity against HIV-1 protease with IC50 of 10.5, 10.3, 12.3 and 6.3μM, respectively. The results indicated that acid treatment of Ginseng extract could produce diverse structures with interesting bioactivity. [Copyright &y& Elsevier]

Abstract: We synthesized dammarane-type triterpene derivatives and evaluated their ability to inhibit HIV-1 and HCV proteases to understand their structure–activity relationships. All of the mono- and di-succinyl derivatives (5a–5f) were powerful inhibitors of HIV-1 protease (IC50 <10μM). However, only di-succinyl (5e) and 2,3-seco-2,3-dioic acid (3b) derivatives similarly inhibited HCV protease (IC50 <10μM). A-nor dammarane-type triterpenes (4a and 4b, IC50 10.0 and 29.9μM, respectively) inhibited HIV-1 protease moderately or strongly, but were inactive against HCV protease. All compounds that powerfully inhibited HIV-1 or HCV protease did not appreciably inhibit the general human proteases, renin and trypsin (IC50 >1000μM). These findings indicated that the mono-succinyl dammarane type derivatives (5a–5d) selectively inhibited HIV-1 protease and that the di-succinyl (5e, 5f) as well as 2,3-seco-2,3-dioic acid (3b) derivatives preferably inhibited both viral proteases. [Copyright &y& Elsevier]

Abstract: Three triterpenoids, 16β-hydroxy-2,3-seco-lup-20(29)-ene-2,3-dioic acid (1), 3β,21β,24-trihydroxy-30-noroleana-12,20(29)-dien-28-oic acid (2) and 16β-hydroxylupane-1,20(29)-dien-3-one (3), along with eleven known triterpenes were isolated from stems of Stauntonia obovatifoliola Hayata subsp. intermedia (Y.C. Wu) T. Chen. Their structures were determined by analysis of HR-EI/FAB-MS and 1D and 2D NMR spectroscopic data and comparison with those in the literature. Ten of the compounds showed inhibitory activity against HIV-1 protease. [Copyright &y& Elsevier]

Background/purpose: Duchenne/Becker muscular dystrophies are X-linked recessive disorders caused by mutations in the Duchenne muscular dystrophy (DMD) gene. We aimed to demonstrate the small mutation patterns of the DMD gene in Taiwanese subjects.Methods: We sequenced all 79 exons of the DMD gene in 33 unrelated Taiwanese families in which large-scale deletions and duplications had been excluded by multiplex ligation-dependent probe amplification.Results: Direct sequencing detected 23 different mutations from 26 families, including 15 novel mutations and eight previously reported ones. The 15 novel mutations consisted of seven substitutions (c.1238C>G [p.S413X], c.2971G>T [p.E991X], c.3172C>T [p.Q1058X], c.7402G>T [p.E2468X], c.8022C>G [p.S2605X], c.10018T>C [p.C3340R], c.10546G>T [p.E3516X]), six small deletions (c.2202delG [p.A668fsX676], c.2268delC [p.F756fsX759], c.4611delT [p.N1537fsX1545], c.4856_4857delAA [p.K1619fsX1621], c.6638delT [p.L2213fsX2220], c.9457delT [p.C3153fsX3154]), and two small insertions (c.4351insA [p.L1451fsX1468], c.10493_10495insAAT [p.L3498X]). Twenty-two of the 23 pathologic changes disrupted the translational reading frame (13 nonsense, 7 frameshift, 2 splice-site change), whereas only one was a missense variant with known pathogenic nature. Two previously reported mutations, c.8038C>T [p.R2680X] and c.10108C>T [p.R3370X] were detected in two and three unrelated families, respectively.Conclusion: Most identified mutations either led to a predictable premature stop codon or resulted in splicing defects, which caused defective function of dystrophin. Our findings extend the mutation spectrum of the DMD gene. Molecular characterization of the affected families is important for genetic counseling and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Derivatives of chlorogenic acid or its analogues were synthesized by coupling protected chlorogenic acid or its analogues with p-octyloxyaniline and selected amino acids. Most of the compounds exhibited significant potency against Cryptococcus neoformans and Candida species with low toxicity to brine shrimps. The 4,5-dihydroxyl groups in the quinic acid moiety were necessary for the activity and introduction of a free amino group increased the inhibitory activity against Aspergillus fumigatus. [Copyright &y& Elsevier]

Abstract: Hepatitis delta virus (HDV) requires the surface antigens of hepatitis B virus (HBV) for packaging and transmission, but replicates its RNA in an HBV-independent fashion. HDV contains a 1.7-kb circular RNA genome that is folded into an unbranched rod-like structure via intramolecular base-pairing, and possesses ribozyme activity. The HDV genome does not encode an RNA-dependent RNA polymerase (RdRp), but is instead replicated by host RNA polymerase(s) via a rolling-circle mechanism. As such, HDV is similar to the viroid plant pathogens. Recent findings suggest that HDV can also undergo template-switching recombination, a well-documented process that has been found in a large number of RdRp-encoding RNA viruses and is thought to affect viral evolution and pathogenesis. This mini-review examines HDV RNA recombination and how it may improve our understanding of the capacities of host RNA polymerases beyond typical DNA-directed transcription, and speculates on the role of host RNA polymerase-directed RNA template-switching in the origin of HDV. [Copyright &y& Elsevier]

Abstract: A gene, mtgA, encoding transglutaminase (TGase) in Streptomyces platensis M5218 was cloned and expressed in Streptomyces lividans. The mtgA gene consisted of an open reading frame of 1254 nucleotides encoding a protein of 418 amino acids with a calculated molecular weight of 46,511Da. The deduced amino acid sequence shows 69.3–77.7% identity to TGases from Streptoverticillium spp., but exhibits less than 35% identity with TGases of Bacillus subtilis and eukaryotic origins. The putative active site, YGCVG, conserved in Streptoverticillium TGases is also present in MtgA. SDS-PAGE and immunoblotting analyses revealed that an intensively stained protein band with a size corresponding to that of mature TGase was present in the culture supernatant of the recombinant strain. The result suggests that the recombinant MtgA may be highly expressed and correctly processed during secretion in the transformed S. lividans JT46. [Copyright &y& Elsevier]

Abstract: Ursolic acid and 2α-hydroxyursolic acid isolated from apple peels were found to show growth inhibitory activity against four tumor cell lines, HL-60, BGC, Bel-7402 and Hela. Structural modifications were performed on the C-3, C-28 and C-11 positions of ursolic acid and the cytotoxicity of the derivatives was evaluated. The SAR revealed that the triterpenes possessing two hydrogen-bond forming groups (an H-donor and a carbonyl group) at positions 3 and 28 exhibit cytotoxic activity. The configuration at C-3 was found to be important for the activity. Introduction of an amino group increased the cytotoxicity greatly. A 3β-amino derivative was 20 times more potent than the parent ursolic acid. The 28-aminoalkyl dimer compounds showed selective cytotoxicity. [Copyright &y& Elsevier]