Teadenol B as a Component of Microorganism-Fermented Tea Extract Inhibited Breast Cancers by Promoting Autophagy.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

LDLR promotes autophagy-mediated cisplatin resistance in ovarian cancer associated with the PI3K/AKT/mTOR signaling pathway.

Autophagy is one of the underlying causes of resistance to many antitumor drugs, including cisplatin (DDP). The low-density lipoprotein receptor (LDLR) is a regulator of ovarian cancer (OC) progression. However, whether LDLR regulates DDP resistance in OC via autophagy-related pathways remains unclear. LDLR expression was measured by quantitative real-time PCR, western blot (WB) and IHC staining. A Cell Counting Kit 8 assay was employed to evaluate DDP resistance and cell viability, and flow cytometry was used to assess apoptosis. WB analysis was employed to evaluate the expression of autophagy-related proteins and PI3K/AKT/mTOR signaling pathway proteins. The autophagolysosomes and the fluorescence intensity of LC3 were observed by transmission electron microscopy and immunofluorescence staining, respectively. A xenograft tumor model was established to explore the role of LDLR in vivo. LDLR was highly expressed in OC cells, which was correlated with disease progression. In DDP-resistant OC cells, high LDLR expression was related to DDP resistance and autophagy. Downregulation of LDLR repressed autophagy and growth in DDP-resistant OC cell lines by activating the PI3K/AKT/mTOR pathway, and these effects were eliminated by an mTOR inhibitor. In addition, LDLR knockdown also reduced OC tumor growth by suppressing autophagy associated with the PI3K/AKT/mTOR pathway. LDLR promoted autophagy-mediated DDP resistance in OC associated with the PI3K/AKT/mTOR pathway, indicating that LDLR might be a new target to prevent DDP resistance in OC patients.

Sleep disorders and non-sleep circadian disorders predict depression: A systematic review and meta-analysis of longitudinal studies.

Patients with depression often suffer from sleep disorders and non-sleep circadian disorders. However, whether they precede and predict subsequent depression is unclear. We conducted a meta-analysis of studies on sleep disorders and non-sleep circadian disorders. We found insomnia, hypersomnia, short and long sleep duration, obstructive sleep apnea, restless legs syndrome and eveningness orientation at baseline all led to subsequent depression. Those with propensity to late meal patterns, heightened levels of cortisol in awakening response and low robustness of rest-activity rhythm at baseline had higher risks for later depression. Among insomnia subtypes, difficulty initiating sleep and difficulty maintaining sleep predicted future depression. Notably, persistent insomnia at baseline contributed to more than two-fold risk of incident depression compared to insomnia. Moreover, insomnia symptom numbers showed dose-dependent relationship with the incident depression. In conclusion, different types of sleep disorders and non-sleep circadian disorders were proven to be risk factors of subsequent depression, and mechanisms underlying the relationship between sleep disorders, non-sleep circadian disorders and subsequent depression should be further elucidated in the future.

Validation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries.

Sanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of view in our previous studies. The bioinformatics prediction showed that the PI3K/Akt/FoxO3a pathway was one of important pathways of SWTX on treatment of coronary heart disease. Based on it, the aim of this study was to evaluate the benefits of SWTX in acute myocardial ischemic-reperfused (MIR) rat in vivo and H9c2 cardiomyoblast cells under oxidative stress induced by H2O2 in vitro, and further investigate the involvement of PI3K/Akt/FoxO3a pathway in these processes. Ex vivo, under physiological conditions, SWTX did not show any modification in the heart rate and contraction amplitude. However, against a MIR injury, SWTX pretreatment provided significant protection, including reduced ST-segment elevation, pathological changes and myocardial infarct size in vivo, meanwhile, some monomers of SWTX showed antioxidant capacity and inhibited cardiomyocytic apoptosis in vitro. The effect was correlated with the activation of the PI3K/Akt/FoxO3a signaling pathway downstream and the regulation of downstream pro-apoptotic Bim of FoxO3a experimental verified by qRT-PCR, Western blot and immunofluorescent assay. In vitro, blocking Akt and p-FoxO3a activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of several active monomers (including quercetin, macelignan,methyleugenol and Santol) of SWTX against H2O2-induced injury. Collectively, these results suggest that SWTX decreases I/R injury, and the PI3K/Akt/FoxO3a pathway takes part in protection during this process, gallogen (G3) and quercetin (G8) of GZ, methyleugenol (R2) and macelignan (R7) of RDK, santol (T1) of TX are responsible at least in part for SWTX's cardioprotection effect.

The efficacy and safety of omega-3 fatty acids on depressive symptoms in perinatal women: a meta-analysis of randomized placebo-controlled trials.

Omega-3 fatty acids (FA), as a nutrient, has been proven effective in major depressive disorder (MDD), however, the results of monotherapy in perinatal depression (PND) remain unclear. To examine the efficacy and safety of omega-3 fatty acids (FA) monotherapy for perinatal depression (PND) compared with placebo. PubMed, Embase, PsycINFO, MEDLINE, Cochrane Library, and CINAHL were searched from inception up to November 2019. The reference lists of relevant review articles and included studies were also reviewed. Randomized placebo-controlled trials examining the efficacy and safety of omega-3 FA monotherapy in perinatal women with depressive symptoms were included. Pooled standard mean differences (SMD) were calculated and random-effects models were adopted for all analyses. Subgroups analyses and meta-regression were performed to quantify characteristics of the subjects and trials influencing the omega-3 response. In addition, meta-regression was conducted to identify the source of heterogeneity. The study protocol was registered at PROSPERO, CRD42020159542. Eight eligible randomized placebo-controlled trials were included involving 638 participants. There was a significant effect of omega-3 FA on perinatal depression. Omega-3 with higher ratio of EPA/DHA (≥1.5) had significant efficacy both in mild-to-moderate pregnant and postpartum depression with low incidence of side effects. Among the included trials reporting adverse effects, there was no significant difference in incidence of gastrointestinal and neurologic events between the omega-3 and placebo groups. There was no evidence of publication bias. Our findings suggested that omega-3 FA significantly improved depressive symptoms in perinatal women regardless of pregnant or postpartum and well-tolerated. Furthermore, the omega-3 response was linked to higher EPA proportion in omega-3 formula and mild- to-moderate depression.

Ansavaricin J, a New Heterocyclic Ring-Fused Streptovaricin from Gene stvP5-Deleted Mutant of Streptomyces spectabilis CCTCC M2017417.

A new ring-fused streptovaricin analogue, named ansavaricin J, was unprecedently isolated from the culture of the genetically modified strains ΔstvP5 which derived from Streptomyces spectabilis CCTCC M2017417. Its structure was elucidated via comprehensive spectroscopic analyses, including 1D- and 2D-NMR tests, and HR-ESI-MS data analysis. Notably, ansavaricin J and E represent the only two reported examples of heterocyclic ring-fused streptovaricins thus far, however, it only showed insignificant antibacterial activities against Staphylococcus aureus.

MicroRNA-9 promotes tumorigenesis and mediates sensitivity to cisplatin in primary epithelial ovarian cancer cells.

MicroRNAs play critical roles in regulating tumor occurrence and drug sensitivity in ovarian cancers. This study aimed to investigate the key members of MicroRNAs (miRNAs) involved in modulating tumor initiation and drug resistance in primary ovarian cancer cells. An in vitro assay based on tumor clonal formation was established to evaluate tumorigenicity and cisplatin sensitivity. By performing real-time polymerase chain reaction, we examined the expression of nine microRNAs associated with the pathology of ovarian cancers in primary ovarian tumor cells, which were surgically resected from 46 patients with distinct sensitivity to platinum-based chemotherapy. MiR-9, miR-145, and miR-429 were expressed significantly higher in drug-sensitive patients (n = 26) than in drug-resistant ones (n = 20), while higher miR-26a expression was found in resistant patients (p < 0.05). In addition, tumor cells from drug sensitive patients were more tumorigenic than those of drug resistance (p = 0.0013). Cisplatin treatment led to a sharp decrease of clonal formation of drug-sensitive cells but showed slight effects on drug resistant cells. Specific anti-miRs were then employed to downregulate the expression of microRNAs in primary tumor cells. Inhibition of miR-9 resulted in decreased clonal formation and sensitivity to cisplatin, while the knockdown of other three microRNAs did not show any influence in tumorigenesis and drug sensitivity. In conclusion, this study showed that in primary ovarian tumor cells, high expression of miR-9 was associated with enhanced tumorigenesis and increased sensitivity of the tumor cells to cisplatin treatment.

Novel second-harmonic-generation-active lead(II) phosphinate based on 2-carboxyethyl(phenyl)phosphinate ligand.

The hydrothermal reaction of PbCl(2) with the achiral 2-carboxyethyl(phenyl)phosphinate ligand (H(2)L) afforded a novel lead(II) phosphinate that contains two enantiomers as a racemic mixture, namely, [Pb(HL)(2)] (Λ- and Δ-1). Each enantiomer features a two-fold symmetrical chiral chain, in which the adjacent Pb(2+) ions are doubly bridged by pairs of HL(-) ligands. The uni-oriented stacking of such 1D chains by edge-to-face π···π interactions results in its crystallization in the chiral C2 space group. Complex 1 shows a second harmonic generation response that is ∼2 times that of KDP (KH(2)PO(4)).

Two polymorphs of (2-carboxyethyl)(phenyl)phosphinic acid.

Two polymorphs of (2-carboxyethyl)(phenyl)phosphinic acid, C(9)H(11)O(4)P, crystallize in the chiral P2(1)2(1)2(1) space group with similar unit-cell parameters. They feature an essentially similar hydrogen-bonding motif but differ slightly in their detailed geometric parameters. For both polymorphs, the unequivocal location of the hydroxy H atoms together with the expected differences in the P-O bond lengths establish unequivocally that both forms contain the S isomer; the protonated phosphinic acid and carboxy O atoms serve as hydrogen-bond donors, while the second phosphinic acid O atom acts as a double hydrogen-bond acceptor and the remaining carboxy O atom is not involved in hydrogen bonding. Thus, an undulating two-dimensional supramolecular layer aggregate is formed based on an R(4)(3)(20) ring unit. Such polymorphism derives from the rotation of the C-C single bonds between the two hydrogen-bond-involved carboxy and phosphinic acid moieties.

Poly[bis-[µ(2)-(dimethyl-aza-nium-yl)methyl-enediphospho-nato]magnesium].

The title compound, [Mg(C(3)H(10)NO(6)P(2))(2)](n), synthesized by a hydro-thermal method, adopts a one-dimensional polymeric chain structure and is isotypic with the previously reported Cd complex based on the ligand N,N-dimethyl-amino-methane-1,1-diphospho-nic acid (H(4)L). The asymmetric unit contains one half Mg(2+) ion and one H(3)L(-) anion. The unique Mg(2+) ion lies on an inversion center and is octa-hedrally coordinated by O atoms from six phospho-nate groups of four different H(3)L(-) anions. Each H(3)L(-) anion, with one protonated N atom and two phospho-nate OH groups, serves as a tridentate ligand. Two of its six phospho-nate O atoms chelate to a Mg(2+) cation in a bidentate fashion, while a third O atom bridges to a neighbouring Mg(2+) ion. The inter-connection of Mg(2+) ions by the H(3)L(-)anions leads to the formation of a polymer chain along the a axis in which the adjacent Mg(2+) ions are doubly bridged by two equivalent H(3)L(-) anions. These discrete chains are further assembled into a three-dimensional supra-molecular network via O-H⋯O and N-H⋯O hydrogen bonds involving the non-coordin-ated phospho-nate O atoms and the protonated N atoms.

DTNBP1 gene is associated with some symptom factors of schizophrenia in Chinese Han nationality.

OBJECTIVE: To study the association of DTNBP1 gene with some symptom factors of schizophrenia. METHODS: A total of 285 unrelated schizophrenic individuals were recruited from December 2004 to January 2009 for genetic analysis, and their symptom factors were assessed based on the Positive and Negative Syndrome Scale (PANSS). The quantitative trait test was performed by the UNPHASED program (version 3.0.12) to investigate the association between scored positive and negative symptoms and the single nucleotide polymorphisms (SNPs) in DTNBP1 gene. RESULTS: The quantitative trait test showed allelic association of rs909706 with the excitement symptom of schizophrenia (P<0.05, adjusted by 10,000 permutations), while the genotype C/G of rs2619539 with a negative symptom, lack of spontaneity and flow of conversation (P<0.05, adjusted by 10,000 permutations). CONCLUSION: DTNBP1 variations are possibly associated with some symptoms of schizophrenia, which could partly explain the relationship between the susceptibility gene DTNBP1 and that disease.

Tris(1,10-phenanthroline-kappa2N,N')cadmium(II) bis(perchlorate) 3.5-hydrate: a water chain stabilized by perchlorate anions.

The title compound, [Cd(C(12)H(8)N(2))(3)](ClO(4))(2).3.5H(2)O, contains a cross-shaped one-dimensional channel along the c axis which encapsulates an ordered water chain. This water chain features a centrosymmetric cyclic water hexamer unit with a chair-like conformation. Neighbouring hexamers are linked by bridging water molecules. The host perchlorate anions recognize and stabilize the guest water chain via three kinds of hydrogen-bond patterns, leading to the formation of a complex one-dimensional {[(H(2)O)(7)(ClO(4))(4)](4-)}(n) anionic chain. One perchlorate acts as a single hydrogen-bond acceptor dangling on the chain, the second perchlorate on the chain serves as a double hydrogen-bond acceptor for only one water molecule to form an R(2)(2)(6) ring, where both entities lie on a twofold axis, while the third perchlorate, which also lies on a twofold axis, accepts two hydrogen bonds from two equivalent water molecules and is involved in the construction of an R(6)(5)(14) ring.

Octanuclear aluminum(III) and iron(III) phosphonate cages encapsulating two Na(I) ions.

Hydrothermal reactions of aluminum(III) nitrate or iron(III) nitrate with N,N-dimethylaminomethane-1,1-diphosphonic acid (H(4)L) and sodium hydroxide lead to two novel isostructural octanuclear metal phosphonate cages encapsulating two Na(I) ions, namely, [Al(8)Na(2)(HL)(2)(H(2)L)(10)(H(2)O)(6)] x 20 H(2)O (1) and [Fe(8)Na(2)(HL)(2)(H(2)L)(10)(H(2)O)(6)] x 22 H(2)O (2). The molecular structure of 1 can be viewed as a three-in-one cluster, in which a central zeolite D6R SBU lookalike aluminophosphonate cage is capped by two symmetry-related aluminophosphonate tetrahedral cages above and below and such a tetrahedral cage, being composed of four zeolite S6R SBU lookalike aluminophosphonate rings, further hexadentately traps one Na(+) ion in its cavity.

Mast cell degranulator compound 48-80 promotes atherosclerotic plaque in apolipoprotein E knockout mice with perivascular common carotid collar placement.

BACKGROUND: Study of the relationship between mast cells and atherosclerosis is mostly dependent on pathological observation and cytology experiments. To investigate the effects of mast cells degranulation on plaque and their possible mechanisms we used apolipoprotein E knockout mice which had been placed perivascular common carotid collar with mast cells degranulator compound 48-80. METHODS: Forty apolipoprotein E knockout mice were fed a western-type diet and operated on with placement of perivascular right common carotid collar. Four weeks after surgery, the mice were intraperitoneally injected with compound 48-80 (0.5 mg/kg) or D-Hanks every other day for 4 times. The serum lipids and activity of tryptase were measured. Tissue sections were stained with hematoxylin and eosin. Corresponding sections were stained with toluidine blue and immunohistochemically with antibodies against macrophage-specific antigen, alpha-smooth muscle actin, interleukin-1beta and von Willebrand factor. Simultaneously, basic fibroblast growth factor was detected by in situ hybridization and immunofluorescence. RESULTS: No pathological change was observed in common carotid non-collar placement but atherogenesis in common carotid collar placement of both groups. There was a significant increase in plaque area ((5.85+/-0.75) x 10(4) vs (0.86+/-0.28) x 10(4) microm(2), P<0.05), the degree of lumen stenosis ((81+/-15)% vs (41+/-12)%, P<0.05), the activity of tryptase in serum ((0.57+/-0.13) U/L vs (0.36+/-0.10) U/L, P<0.05), and the percentage of degranulated mast cells ((80.6+/-17.8)% vs (13.5+/-4.1)%, P<0.05). The expressions of macrophage-specific antigen, alpha-smooth muscle actin, interleukin-1beta, basic fibroblast growth factor and the density of neovessel in plaque were more in the compound 48-80 group than in the control group. CONCLUSIONS: Perivascular common carotid collar placement can promote atherosclerotic plaque formation in apolipoprotein E knockout mice. Compound 48-80 increases plaque area and the degree of lumen stenosis by the mechanism that compound 48-80 promotes proliferation of smooth muscle cells and aggregation of macrophages. Compound 48-80 promotes angiogenesis in plaque. The mechanism is potentially that compound 48-80 increases the expressions of basic fibroblast growth factor mRNA and protein in plaque. Compound 48-80 enhances the expression of interleukin-1beta in plaque.

Dibromidobis(1,10-phenanthroline-κN,N')cadmium(II).

The title compound, [CdBr(2)(C(12)H(8)N(2))(2)], synthesized by the hydro-thermal reaction of Cd(CH(3)COO)(2)·2H(2)O with NaBr and 1,10-phenanthroline, has the Cd(II) cation coordinated by two Br(-) anions and four N atoms from two 1,10-phenanthroline ligands in a distorted octa-hedral geometry. The crystal packing is stabilized by inter-molecular π-π inter-actions with centroid-centroid distances 3.572 (1) and 3.671 (1) Štogether with C-H⋯Br hydrogen bonds.

[The epidemic situation of human rabies from 1984 to 2002 and its preventive measures in China].

OBJECTIVE: To summarize and analyze the epidemic situation of human rabies from 1984 to 2002 in China, and to explore the possible factors causing the increase of cases so as to provide evidence for preventive and control measures. METHOD: National and some provincial data on the prevalence of rabies during 1984 to 2002 were collected and analyzed. RESULTS: From 1984 to 1989, the annual reported cases were between 4 000 and 6 000 but decreased after 1990. In 1996, the reported cases decreased to the lowest level from 3 520 in 1990 to 159. However, number of reported cases has been continuously increasing since 1998 which reached 1 122 in 2002, a 7.06 times increase as compared to the number in 1996. The epidemic areas were mainly located in the southeast and southwest parts of the country, such as Sichuan, Hunan, Guangxi, Guangdong, Anhui, Fujian, etc. Furthermore, there was no significant seasonal distribution as it showed before. CONCLUSION: Such facts as the increasing numbers of dogs, low inoculation rate to dogs, poor control on the quality of rabies vaccine, mistreatment to the wounds, and lacking good cooperation between different official departments regarding rabies control might serve as important factors responsible for the recurrence of rabies. Therefore, it is necessary to focus on the above mentioned points and to take comprehensive preventive measures to bring down the prevalence of rabies in China.

[Detection of cell-free fetal DNA in the urine of pregnant women by nested polymerase chain reaction].

OBJECTIVE: To investigate the clinical feasibility of fetal sex determination by using nested polymerase chain reaction (PCR) to detect cell-free fetal DNA in the urine of pregnant women. METHODS: The urine specimens of 40 healthy predelivery women were centrifuged. The DNA in the specimens of supernatant was extracted by using of QIAamp Viral RNA Mini Kits. Nested PCR was used to specifically amplify the SRY gene, 300 bp in length, on Y chromosome in order to detect the fetal DNA from the women bearing male fetuses. One specimen of normal man's urine and one specimen of non-pregnant woman's urine were used as controls for each specimen from pregnant women. The results were confirmed by the sexes of neonates examined after birth. RESULTS: Amplified band of SRY was found in 6 specimens. Sex examination after delivery showed 21 male neonates and 19 female neonates. The positive rate of detection of SRY gene was 28.6% (6/21) and the false negative rate was 71.4%, and false positive rate was 0. Five out of the 6 cases with positive results showed positive 2 times and one out of the 6 cases only showed positive at the second time. CONCLUSION: There is cell-free fetal DNA in the urine of pregnant women. Nested PCR is useful in detection of fetal sex, however, still with a rather low positive rate.

[Determination of nanchangmycin and meilingmycin by high performance liquid chromatography].

A high performance liquid chromatographic method had been established for the separation and determination of two antibiotics produced by Streptomyces nanchangensis, polyether nanchangmycin and 16-membered macrolide meilingmycin. The latter is composed of several components. The operating conditions were Waters XTerra RP18 column (3.9 mm i.d. x 150 mm, 5 microns) at 25 degrees C, mobile phase linear gradient elution of acetonitrile-water with 57:43 (volume ratio) during 0 min-30 min, 70:30 during 30 min-32 min, 80:20 during 32 min-34 min, 90:10 during 34 min-50 min at a flow rate of 0.8 mL/min, and photodiode array detector at 234 nm. This method is accurate, rapid and simple, and can be used for the integrated analysis of the two different natural compounds, polyethers and macrolides.