Letrozole for patients with polycystic ovary syndrome: A retrospective study.

This retrospective study investigated the efficacy and safety of letrozole for patients with polycystic ovary syndrome (PCOS).Totally, 136 cases of infertility women with PCOS were analyzed. Of those, 68 patients received letrozole, and were assigned to Letrozole group. The other 68 cases received clomiphene, and were assigned to clomiphene group. Patients in both groups were treated up to 5 treatment cycles. The primary endpoint included infant outcomes. The secondary endpoints consisted of the number of women in conception, pregnancy, pregnancy loss, and ovulation. In addition, any kinds of adverse events were also recorded.Cases in the Letrozole group did not show better outcomes neither in primary endpoint (live birth, P = .11; birth weight, P = .95; infant gender, P = .85), nor in secondary endpoints (the number of women in conception, P = .07; pregnancy, P = .12; pregnancy loss, P = .47; pregnancy loss in first trimester, P = .70; and ovulation, P = .09), compared with cases in the clomiphene group. Moreover, no adverse events differ significantly between 2 groups.This study demonstrated that the efficacy of letrozole is not superior to the clomiphene in patients with PCOS.

Percutaneous nerve electrical stimulation for fatigue caused by chemotherapy for cervical cancer.

This retrospective study investigated the effectiveness of percutaneous nerve electrical stimulation (PNES) for fatigue caused by chemotherapy for cervical cancer survivors.Totally, 83 cases of fatigue caused by chemotherapy for cervical cancer survivors were analyzed. All these cases were assigned to a treatment group (n = 43), and a control group (n = 40). Patients in the treatment group received PNES, while the subjects in the control group were on waiting list. The treatment was applied once daily for a total of 6 weeks. The primary endpoint was fatigue. It was evaluated by the Multidimensional Fatigue Inventory (MFI), and Fatigue Questionnaire (FQ). The secondary endpoints consisted of anxiety and depression. They were measured by the Hospital Anxiety and Depression Scale (HADS). All outcomes were measured before and after 6-week treatment.After treatment, PNES did not show significant difference in fatigue relief, measured by MFI (General fatigue, P = .31; Physical fatigue, P = .44; Activity, P = .36; Motivation, P = .55; Mental fatigue, P = .49), and FQ (Mental fatigue, P = .29; Physical fatigue, P = .35); and the reduction of anxiety and depression, measured by the HADS (Anxiety, P = .21; Depression, P = .17) after 6 weeks treatment between 2 groups.This study demonstrated that PNES may not benefit for cervical cancer survivors with fatigue caused by chemotherapy after 6-week treatment.

The effects of rhEPO intervention for perinatal intrauterine herpes virus infection on preventing brain injury in preterm infants.

The ability of recombinant human erythropoietin (rhEPO) to protect preterm infants against perinatal intrauterine herpes virus infection-induced brain injury was studied. In total, 120 women infected with perinatal intrauterine herpes virus were randomized into four groups: A, B, C and D, and were given 1,500 IU (mother, pre-partum), 3,000 IU (mother, pre-partum), 250 IU/kg (infant, post-natal), and no rhEPO, respectively. Hemoglobin (Hb), reticulocyte (Ret), hematocrit (Hct), neuron specific enolase (NSE), myelin basic protein (MBP), and S100 protein B (S100B) levels were measured immediately (T0) and at 1 week (T1), 2 weeks (T2), and 4 weeks (T3) post-delivery. Linear regression analysis was performed to analyze inter-indicator correlation, and ROC risk models were established to determine the predictive value of Hb, Ret and Hct for brain injury immediately after delivery. The brain injury incidence rate of group A (10%) was significantly lower than group D (33.3%) and group B (6.7%) significantly lower than groups C (26.7%) and D. At T0, Hb, Ret and Hct in groups A and B were significantly higher than in group C and D, while from T1 to T3, groups A, B and C showed significantly higher values than group D. NSE, MBP and S100B showed an inverse trend, with groups A and B lower at T0 and groups A, B and C lower from T1-T3. Hb and NSE, MBP and S100B were negatively correlated, while no correlation was found between Ret and NSE, MBP and S100B. Finally, Hct and NSE, MBP and S100B were negatively correlated. The optimal cut-off values for Hb and Hct for brain injury diagnosis immediately post-partum were 170 g/l (sensitivity 99%, specificity 95.7%) and 28.5% (sensitivity 79.4%, specificity 100%), respectively. Ret did not show predictive value. In conclusion, pre-partum rhEPO treatment showed greater protective effects than post-natal administration, and this may be the regulation of Hb and Hct levels in post-natal preterm infants. In addition, a dose-dependent effect was displayed.

Molecular cloning, sequence analysis and phylogeny of first caudata g-type lysozyme in axolotl (Ambystoma mexicanum).

Lysozymes are key proteins that play important roles in innate immune defense in many animal phyla by breaking down the bacterial cell-walls. In this study, we report the molecular cloning, sequence analysis and phylogeny of the first caudate amphibian g-lysozyme: a full-length spleen cDNA library from axolotl (Ambystoma mexicanum). A goose-type (g-lysozyme) EST was identified and the full-length cDNA was obtained using RACE-PCR. The axolotl g-lysozyme sequence represents an open reading frame for a putative signal peptide and the mature protein composed of 184 amino acids. The calculated molecular mass and the theoretical isoelectric point (pl) of this mature protein are 21523.0 Da and 4.37, respectively. Expression of g-lysozyme mRNA is predominantly found in skin, with lower levels in spleen, liver, muscle, and lung. Phylogenetic analysis revealed that caudate amphibian g-lysozyme had distinct evolution pattern for being juxtaposed with not only anura amphibian, but also with the fish, bird and mammal. Although the first complete cDNA sequence for caudate amphibian g-lysozyme is reported in the present study, clones encoding axolotl's other functional immune molecules in the full-length cDNA library will have to be further sequenced to gain insight into the fundamental aspects of antibacterial mechanisms in caudate.

Structural and functional characterization of CATH_BRALE, the defense molecule in the ancient salmonoid, Brachymystax lenok.

Thick-lipped lenok, Brachymystax lenok is one of the ancient fish species in China and northeast Asia countries. Due to the overfishing, the population of lenok has been declined significantly. Cathelicidins are innate immune effectors that possess both bactericidal activities and immunomodulatory functions. This report identifies and characterizes the salmonoid cathelicidin (CATH_BRALE) from this ancient fish. It consists of open reading frame (ORF) of 886 bp encoding the putative peptide of 199 amino acids. Sequence alignment with other representative salmonid cathelicidins displayed two distinctive features of current lenok cathelicidin: high level of arginine, resulting in high positive charge and glycine residues, which is significantly different from most acknowledged types of cathelicidins; and the six-aminoacid tandem repeated sequence of RPGGGS detected in a variable number of copies among fish cathelicidins, suggesting the existence of a genetically unstable region similar to that found in some mammalian cathelicidins. Expression of CATH_BRALE is predominantly found in gill, with lower levels in the gastrointestinal tract and spleen. The homology modeled structure of CATH_BRALE exhibits structural features of antiparallel b-sheets flanked by a-helices that are representative of small cationic cathelicidin family peptides. CATH_BRALE possesses much stronger antimicrobial activity against gram-negative bacteria than that of the human ortholog, LL-37. The growth of two typical fish bacterial pathogens, gram-negative bacterium of Aeromonas salmonicida and Aeromonas hydrophila was substantially inhibited by synthetic CATH_BRALE, with both MICs as low as 9.38 mM.

[Progress in cathelicidins antimicrobial peptides research].

Cathelicidins are a family of multi-functional antimicrobial peptides found in almost all types of vertebrates, where they play vital roles in the immune system. As they possess broad-spectrum antimicrobial properties, cathelicidins are not only strongly resistant to Gram-positive and Gram-negative bacteria, fungi, and viruses, but they are also active against many antibiotic-resistant clinical bacteria, adopting a special antimicrobial mechanism that is unlikely to lead to microbial resistance. Cathelicidins likewise possess simple structures, and low hemolytic and cytotoxic activities. Collectively, these features suggest potentially novel and exciting prospects for cathelicidins' application in medicine. Here, we review the structures, classification, activities, mechanisms, as well as prospective developments in the usage and application of cathelicidin antimicrobial peptides.

Cathelicidin-BF, a snake cathelicidin-derived antimicrobial peptide, could be an excellent therapeutic agent for acne vulgaris.

Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules in innate immunity. Cathelicidin-BF has been purified from the snake venoms of Bungarus fasciatus and it is the first identified cathelicidin antimicrobial peptide in reptiles. In this study, cathelicidin-BF was found exerting strong antibacterial activities against Propionibacterium acnes. Its minimal inhibitory concentration against two strains of P. acnes was 4.7 µg/ml. Cathelicidin-BF also effectively killed other microorganisms including Staphylococcus epidermidis, which was possible pathogen for acne vulgaris. Cathelicidin-BF significantly inhibited pro-inflammatory factors secretion in human monocytic cells and P. acnes-induced O2.- production of human HaCaT keratinocyte cells. Observed by scanning electron microscopy, the surfaces of the treated pathogens underwent obvious morphological changes compared with the untreated controls, suggesting that this antimicrobial peptide exerts its action by disrupting membranes of microorganisms. The efficacy of cathelicidin-BF gel topical administering was evaluated in experimental mice skin colonization model. In vivo anti-inflammatory effects of cathelicidin-BF were confirmed by relieving P. acnes-induced mice ear swelling and granulomatous inflammation. The anti-inflammatory effects combined with potent antimicrobial activities and O2.- production inhibition activities of cathelicidin-BF indicate its potential as a novel therapeutic option for acne vulgaris.

Gene cloning, expression and characterization of avian cathelicidin orthologs, Cc-CATHs, from Coturnix coturnix.

Cathelicidins comprise a family of antimicrobial peptides sharing a highly conserved cathelin domain, which play a central role in the early innate host defense against infection. In the present study, we report three novel avian cathelicidin orthologs cloned from a constructed spleen cDNA library of Coturnix coturnix, using a nested-PCR-based cloning strategy. Three coding sequences containing ORFs of 447, 465 and 456 bp encode three mature antimicrobial peptides (named Cc-CATH1, 2 and 3) of 26, 32 and 29 amino acid residues, respectively. Phylogenetic analysis indicated that precursors of Cc-CATHs are significantly conserved with known avian cathelicidins. Synthetic Cc-CATH2 and 3 displayed broad and potent antimicrobial activity against most of the 41 strains of bacteria and fungi tested, especially the clinically isolated drug-resistant strains, with minimum inhibitory concentration values in the range 0.3-2.5 µm for most strains with or without the presence of 100 mm NaCl. Cc-CATH2 and 3 showed considerable reduction of cytotoxic activity compared to other avian cathelicidins, with average IC(50) values of 20.18 and 17.16 µm, respectively. They also exerted a negligible hemolytic activity against human erythrocytes, lysing only 3.6% of erythrocytes at a dose up to 100 µg·mL(-1) . As expected, the recombinant Cc-CATH2 (rCc-CATH2) also showed potent bactericidal activity. All these features of Cc-CATHs encourage further studies aiming to estimate their therapeutic potential as drug leads, as well as coping with current widespread antibiotic resistance, especially the new prevalent and dangerous 'superbug' that is resistant to almost all antibiotics.

Molecular cloning and characterization of novel cathelicidin-derived myeloid antimicrobial peptide from Phasianus colchicus.

Cathelicidins were initially characterized as a family of antimicrobial peptides. Now it is clear that they fulfill several immune functions in addition to their antimicrobial activity. In the current work, three cDNA sequences encoding pheasant cathelicidins were cloned from a constructed bone marrow cDNA library of Phasianus colchicus, using a nested-PCR-based cloning strategy. The three deduced mature antimicrobial peptides, Pc-CATH1, 2 and 3 are composed of 26, 32, and 29 amino acid residues, respectively. Unlike the mammalian cathelicidins that are highly divergent even within the same genus, Pc-CATHs are remarkably conserved with chicken fowlicidins with only a few of residues mutated according to the phylogenetic analysis result. Synthetic Pc-CATH1 exerted strong antimicrobial activity against most of bacteria and fungi tested, including the clinically isolated (IS) drug-resistant strains. Most MIC values against Gram-positive bacteria were in the range of 0.09-2.95 µM in the presence of 100mM NaCl. Pc-CATH1 displayed a negligible hemolytic activity against human erythrocytes, lysing 3.6% of erythrocytes at 3.15 µM (10 µg/ml), significantly higher than the corresponding MIC. Pc-CATH1 was stable in the human serum for up to 72 h, revealing its extraordinary serum stability. These specific features of Pc-CATH1 may make its applications much wider given the potency and breadth of the peptide's bacteriocidal capacity and its resistance towards serum and high-salt environments.