[Clinical efficacy of posterior femoral muscle flaps combined with posterior femoral cutaneous nerve nutrient vessel flap and closed lavage in the treatment of stage â £ ischial tuberosity pressure ulcers].

Objective: To explore the clinical efficacy of posterior femoral muscle flaps combined with posterior femoral cutaneous nerve nutrient vessel flap and closed lavage in the treatment of stage Ⅳ ischial tuberosity pressure ulcers. Methods: This study was a retrospective observational study. From March 2021 to March 2022, 15 patients with stage Ⅳ ischial tuberosity pressure ulcers who met the inclusion criteria were admitted to Dezhou Dongcheng Hospital, including 11 males and 4 females, aged 31 to 72 years. The pressure ulcer wound size ranged from 6.0 cm×4.5 cm to 10.0 cm×6.0 cm, with cavity diameters of 10-14 cm. Five cases were complicated with ischial tuberosity bone infection. After clearing the lesion, the biceps femoris long head muscle flap with an area of 10.0 cm×4.0 cm-18.0 cm×5.0 cm and the semitendinosus muscle flap with an area of 8.0 cm×4.0 cm-15.0 cm×5.0 cm combined with the posterior femoral cutaneous nerve nutrient vessel flap with an area of 6.5 cm×5.5 cm-10.5 cm×6.5 cm was transplanted to repair the pressure ulcer wound. The flap donor area was directly sutured, and the closed lavage with tubes inserted into the wound cavity was performed for 2-3 weeks. The postoperative survival of the muscle flaps and skin flaps, the wound healing of the donor and recipient areas were observed. The recurrence of pressure ulcers, the appearance and texture of flaps, and scar conditions of the donor and recipient areas were followed up. Results: All the muscle flaps and skin flaps in the 15 patients successfully survived after surgery. Two patients experienced incisional dehiscence at one week after surgery due to improper turning over, during which the incision in the recipient area was pressed on, and the wounds healed after dressing changes of 3 to 4 weeks; the wounds in the donor and recipient areas healed well in the other patients. All patients received follow-up after surgery. During the follow-up period of 6 to 12 months, none of the patients experienced pressure ulcer recurrence, and the texture, color, and thickness of the skin flaps closely resembled those of the surrounding skin at the recipient site, with only linear scar left in the donor and recipient areas. Conclusions: When using the posterior femoral muscle flaps combined with the posterior femoral cutaneous nerve nutrient vessel flap and closed lavage to treat stage Ⅳ ischial tuberosity pressure ulcers, the tissue flap can be used to fully fill in the dead space of the pressure ulcers. After treatment, the wound heals well, the appearance of the donor and recipient areas is better, and the pressure ulcers are less prone to reoccur.

[Chaihu Guizhi decoction produces antidepressant-like effects via sirt1-p53 signaling pathway].

OBJECTIVE: To investigate the mechanism of the antidepressant-like effects of Chaihu Guizhi decoction (CGD). OBJECTIVE: Chaihu Guizhi decoction at the daily dose of 17 g/kg and solvent vehicle were administered by gavage in 12 and 14 male C57BL/6J mice for 7 consecutive days, respectively. Forced swimming test (FST), elevated plus maze (EPM) test, open field test (OFT) and novelty-suppressed feeding test (NSF) were performed to assess the depression- and anxiety-like behaviors and motor ability of the mice. We further used chronic social defeat stress (CSDS) and social interaction test to evaluate the antidepressant-like effects of CGD in comparison with the solvent vehicle. Western blotting and RT-qPCR were performed to detect the expressions of sirt1, p53, acetylated p53, and the neuron plasticity-related genes including synapsin I (Syn1), Rab4B, SNAP25 and tubulin beta4b in the hippocampus of the mice. OBJECTIVE: In FST, the immobility time of CGDtreated mice was decreased significantly (P < 0.05); no significant differences were found in the performances in EPM, NSF and OFT tests between the two groups. In social interaction test, the mouse models of CSDS treated with CGD showed significantly increased time in the interaction zone (P < 0.05). Compared with those in the vehicle group, the CGD-treated mouse models exhibited significantly increased protein level of SIRT1 and decreased p53 acetylation (P < 0.05) with up-regulated synapsin I mRNA expression in the hippocampus (P < 0.05); no significant difference were found in Rab (P=0.813), SNAP (P=0.820), or Tubb mRNA expressions (P=0.864) between the two groups. OBJECTIVE: CGD produces antidepressant-like effects in mice possibly through the sirt1-p53 signaling pathway and synaptic plasticity.

Patient-derived organoids of non-small cells lung cancer and their application for drug screening.

Patient-derived organoids (PDOs) are emerging as preclinical models with promising values in personalized cancer therapy. The purpose of this study was to establish a living biobank of PDOs from patients with non-small cell lung cancer (NSCLC) and to study the responses of PDOs to drugs. PDOs derived from NSCLC were cultured in vitro, and then treated with natural compounds including chelerythrine chloride, cantharidin, harmine, berberine and betaine with series of concentrations (0.5-30 µM) for drug screening. Phenotypic features and treatment responses of established PDOs were reported. Cell lines (H1299, H460 and H1650) were used for drug screening. We successfully established a living NSCLC organoids biobank of 10 patients, which showed similar pathological features with primary tumors. Nine of the 10 patients showed mutations in EGFR. Natural compounds chelerythrine chloride, cantharidin and harmine showed anticancer activity on PDOs and cell lines. There was no significant difference in the 95% confidence interval (CI) for the IC50 value of chelerythrine chloride between PDOs (1.56-2.88 µM) and cell lines (1.45-3.73 µM, p>0.05). PDOs were sensitive to berberine (95% CI, 0.092-1.55 µM), whereas cell lines showed a resistance (95% CI, 46.57-2275 µM, p<0.0001). PDOs had a higher IC50 value of cantharidin, and a lower IC50 value of harmine than cell lines (p<0.05, 7.50-10.45 µM and 4.27-6.50 µM in PDOs, 3.07-4.44 µM and 4.69-544.99 µM in cell lines, respectively). Both PDOs and cell lines were resistant to betaine. Chelerythrine chloride showed the highest inhibitory effect in both models. Our study established a living biobank of PDOs from NSCLC patients, which might be used for high-throughput drug screening and for promising personalized therapy design.

[Relationship between the level of estrogen, calcium and phosphorus concentration in serum with benign paroxysmal positional vertigo].

Objective:To investigate relationship between the level of estrogen, calcium and phosphorus concentration in serum with benign paroxysmal positional vertigo(BPPV). Method:A total of 84 patients with idiopathic BPPV were enrolled in the experimental group, including 32 non-menopausal women, 24 menopausal women, and 28 males; 83 healthy people without vertigo and vestibular disease were selected as the control group consisted with 32 non-menopausal women, 24 menopausal women and 27 males. The levels of estradiol, serum calcium and serum inorganic phosphorus were measured in all participants. The difference of estrogen level, serum calcium and serum inorganic phosphorus concentration between the experimental group and the control group was analyzed by t test. Result:The total number, age distribution and gender composition of the experimental group and the control group were basically paired, and the age difference was not statistically significant (P=0.71). The overall estrogen level in the experimental group was lower than that in the control group (P<0.01). Among them, the female group's estrogen level, menopausal female estrogen level and male estrogen level in the experimental group were lower than the control group (P<0.01); there was no significant difference in serum calcium and serum inorganic phosphorus concentration between the experimental group and the control group (P=0.55, 0.11, respectively). Conclusion:The decrease of estrogen level may be a risk factor for idiopathic BPPV. The relationship between serum calcium and serum inorganic phosphorus concentration and BPPV needs further study.

[Effect of Anluohuaxianwan on the expression of matrix metalloproteinases and their inhibitors in rat liver with fibrosis].

Objective: To investigate the effect of anluohuaxianwan (ALHXW) using rat model of carbon tetrachloride (CCl(4)) induced liver fibrosis on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Methods: Thirty-six male Wistar rats were randomly assigned into control, model and treatment groups. Rats in the model and treatment groups were injected intraperitoneally with 40% CCl(4) (2 ml/kg), and the control group were given isotonic saline twice a week for six weeks. Meanwhile, the treatment group were gavaged with ALHXW solution daily (concentration 0.15 g/ml, 9.9 ml/kg) for 6 weeks, while the control and model groups were given isotonic saline once a day for 6 weeks. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at the end of third and sixth week. At the end of six weeks, liver tissues were harvested for histopathological evaluation and the detection of mRNA and protein expression levels of MMP-2/13 and TIMP-1/2. According to different data, LSD method, parametric (one-way ANOVA) and non-parametric tests (Kruskal-Wallis H-test and Mann-Whitney U test) were used for statistical analysis. Results: Compared with the model group, ALHXW markedly alleviated liver injury in the treatment group, and thereby improved the general state of rats, liver and spleen morphological characteristics, and ALT and AST levels. Histopathological examination demonstrated that the extent of liver fibrosis was improved (2.75 ± 0.75 vs. 3.55 ± 0.69, P = 0.015) in the treatment group as compared with the model group. The mRNA and protein expression levels of MMP-13 in the treatment group were significantly higher than that of the model group (mRNA: 10.50 ± 7.64 vs. 4.40 ± 2.97, P = 0.029. Protein: 1.15 ± 0.09 vs. 0.78 ± 0.21, P = 0.016), whereas the mRNA and protein expression levels of MMP-2, TIMP-1/2 in the treatment group were significantly lower than that of the model group (mRNA: 4.55 ± 3.29 vs. 7.83 ± 4.19, P = 0.048; 1.66 ± 0.73 vs. 3.69 ± 2.78, P = 0.023; 2.25 ± 1.16 vs. 3.41 ± 1.51, P = 0.049; respectively. Protein: 0.44 ± 0.11 vs. 0.65 ± 0.05, P = 0.03; 0.69 ± 0.06 vs. 1.07 ± 0.21, P = 0.016; 0.46 ± 0.09 vs. 0.81 ± 0.13, P = 0.003; respectively). Conclusion: ALHXW exerts anti-liver fibrosis effects mainly by improving liver function, inhibiting the activation of hepatic stellate cells, enhancing the expression of MMP-13, and inhibiting the expression of MMP-2 and TIMP-1/2.

Probiotic Bacillus enhance the intestinal epithelial cell barrier and immune function of piglets.

Bacillus is widely used in the livestock industry. This study was designed to evaluate the effects of probiotic Bacillus amyloliquefaciens SC06 (Ba), originally isolated from soil, in piglets diet as an alternative to antibiotics (aureomycin), mainly on intestinal epithelial barrier and immune function. Ninety piglets were divided into three groups: G1 (containing 150 mg/kg aureomycin in the diet); G2 (containing 75 mg/kg aureomycin and 1×108 cfu/kg Ba in the diet); G3 (containing 2×108 cfu/kg Ba in the diet without any antibiotics). The results showed that, compared with the antibiotic group (G1), villus length, crypt depth and villus length/crypt depth ratio of intestine significantly increased in the G2 and G3 groups. In addition, intestinal villi morphology, goblet-cell number, mitochondria structure and tight junction proteins of intestinal epithelial cells in G2 and G3 were better than in G1. The relative gene expression of intestinal mucosal defensin-1, claudin3, claudin4, and human mucin-1 in G3 was significantly lower, while the expression of villin was significantly higher than in the antibiotic group. Probiotic Ba could significantly decrease serum interferon (IFN)-α, IFN-γ, interleukin (IL)-1ß, and IL-4 levels, whereas increase tumour necrosis factor (TNF)-α and IL-6 secretion. Ba could also significantly decrease cytokines TNF-α, IFN-γ, IL-1ß, and IL-4 level in liver, whereas it significantly increased IFN-α. Furthermore, replacing antibiotics with Ba also significantly down-regulated gene expression of TNF and IL-1α in intestinal mucosa, but up-regulated IL-6 and IL-8 transcription. Dietary addition of Ba could significantly reduce the gene expression of nuclear factor kappa beta (NFκB)-p50 and Toll-like receptor (TLR)6, while there was no significant difference for that of myeloid differentiation primary response 88, TNF receptor-associated factor-6, nucleotide-binding oligomerisation domain-containing protein 1, TLR2, TLR4, and TLR9. Taken together, our findings demonstrated that probiotic Ba could increase the intestinal epithelial cell barrier and immune function by improving intestinal mucosa structure, tight junctions and by activating the TLRs signalling pathway.

[Clinical abservations of pulmonary surfactant' s autologous transfusion in massive lung lavage].

Objective: Investigate the pulmonary surfactant autotransfusion effect on the recovery of respiratory function in patients with whole lung lavage, to provide theoretical basis for the clinical application. Methods: We taken 30 patients of pneumoconiosis treated by whole lung lavage as the subjects. We extracted the pulmonary surfactant from lavage fluid, after single postoperative lung lavage for the first time; after one weeks when the second times of lung lavage were performed to the other side of the lung of patients, we put PS into the right side. We taken the patients the second times of lung lavage who were put PS into the right side as returning group, the first times of lung lavage who were not put PS into as on returning group. We observed indi-cators, such as expiratory resistance, respiratory work, lung compliance, airway pressure, PO(2), the pulmonary function recovery time and other indicators, comparing with the changes of pulmonary function before lung la-vage for the first time and at 0、60、90、120 min after the pulmonary surfactant autotransfusion. Results: Com-pared with the no returning group, the expiratory resistance of the returning group decreased significantly at 90 min、120 min after the pulmonary surfactant autotransfusion; the respiratory work and airway pressure of the re-turning group decreased significantly at 60、90、120 min after the pulmonary surfactant autotransfusion, there was statistically significant in the difference between different groups (P<0.05, P<0.01). Compared with the no returning group, the lung compliance and the PO(2) of the returning group increased significantly at 60 min、90 min、120 min after the pulmonary surfactant autotransfusion, there was statistically significant in the difference between different groups (P<0.05, P<0.01). The lung function recovery time of returning group was (155.7 ± 35.2) min, the lung function recovery time of no returning group was (183.71±41.81) min, there was statistical-ly significant in the difference between different groups (P<0.05). Compared with the no returning, there were not statistically significant in the difference of the Heart rate、the systolic blood pressure and the diastolic blood pressure about the returning at 60、90、120 min after the pulmonary surfactant autotransfusion.There was no ad-verse reactions such as pulmonary infection, pulmonary infection and so on. Conclusion: The pulmonary surfac-tant autotransfusion may reduce expiratory resistance, work of breathing, airway pressure; improve lung compliance, alveolar ventilation function; increase oxygen partial pressure and decrease the surgery recovery time in patients with pneumoconiosis.

[Effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk. Results: ①With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) (P=0.886) in high risk groups respectively. ②Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34(+) cell number and transfused CD3(+) cell number. DFS was significant lower in primary AML than that in secondary AML (P=0.006) and also lower in MRD positive than that in MRD negative (P=0.003) . The accumulative relapse was significant higher in CR(2) compared to that in CR(1) (P=0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML (P=0.004) and also higher in MRD positive compared to that in MRD negative (P=0.010) . ③Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM. Conclusion: Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR(1) and CR(2) patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.

Molecular cloning and characterization of a C-type lectin in yellow catfish Tachysurus fulvidraco.

This study represents the first report of a C-type lectin (ctl) in yellow catfish Tachysurus fulvidraco. The complete sequence of ctl complementary (c)DNA consisted of 685 nucleotides. The open reading frame potentially encoded a protein of 177 amino acids with a calculated molecular mass of c.y 20.204 kDa. The deduced amino-acid sequence contained a signal peptide and a single carbohydrate recognition domain with four cysteine residues and GlnProAsp (QPD) and TrpAsnAsp (WND) motifs. Ctl showed the highest identity (56.0%) to the predicted lactose binding lectin from channel catfish Ictalurus punctatus. Quantitative real-time (qrt)-PCR analysis showed that ctl messenger (m)RNA was constitutively expressed in all examined tissues in normal fish, with high expression in trunk kidney and head kidney, which was increased following Aeromonas hydrophila challenge in a duration-dependent manner. Purified recombinant Ctl (rCtl) from Escherichia coli BL21 was able to bind and agglutinate Gram-positive and Gram-negative bacteria in a calcium-dependent manner. These results suggested that Ctl might be a C-type lectin of T. fulvidraco involved in innate immune responses as receptors (PRR).

Antimicrobial and antitumor activity and diversity of endophytic fungi from traditional Chinese medicinal plant Cephalotaxus hainanensis Li.

Endophytes from Cephalotaxus hainanensis Li, an important source of anti-leukemia drugs, have not been widely explored. In this study, 265 endophytic fungal isolates from C. hainanensis Li were screened for antimicrobial activities against tilapia, banana, rice, and rape and for antitumor activities against human leukemia cell lines (K562, NB4, and HL-60). Diversity was also analyzed. The results showed that 17.7% of the endophytic fungi had antimicrobial activities against at least three different test microbes, and activity against Fusarium oxysporum RKY102 was the highest at 15.8%. Cytotoxicity against at least one tumor cell line tested was observed in 18.5% of the endophytic fungi; with the highest value of 10.6% against K562. The endophytic fungal strains also showed relatively high activities against K562, NB4, and HL-60 while relatively fewer strains were cytotoxic against the human hepatic Hep-G2 and colon LoVo cancer cell lines. Thirty endophytic fungal strains showed both high antimicrobial and antitumor activities. Moreover, the analyses of the diversity of the 30 highly active strains showed they belonged to 20 species from 14 genera, and this is the first report of endophytic fungi Albonectria rigidiuscula, Colletotrichum magnisporum, and Nemania diffusa being isolated from Cephalotaxus plants. These findings suggest that natural antibacterial products for humans and tilapia; antifungal compounds for rice, rape, and banana; and antitumor compounds for leukemia therapy could be isolated from fungal strains derived from C. hainanensis Li.

Effect of Rhizoma paridis total saponins on apoptosis of colorectal cancer cells and imbalance of the JAK/STAT3 molecular pathway induced by IL-6 suppression.

We observed the influence of different concentrations of Rhizoma paridis total saponins (RPTS) on the apoptosis of colorectal cancer cells and explored the internal mechanism involved. We determined whether RPTS influences the interleukin-6 (IL-6)/Janus kinase (JAK)-signal transducer and activator of transcription-3 (STAT3) apoptosis molecular pathway and looked for colon cancer-related signal transduction pathways or targets inducing apoptosis. We also cultured SW480 colorectal cancer cells using different concentrations of RPTS (10, 20, 40, and 80 µg/ mL), and observed the effect of RPTS on SW480 cell morphology under a fluorescence inverted microscope. We detected serum IL-6 using the polymerase chain reaction and the expression of JAK-STAT3 protein by western blot. After treating SW480 with RPTS and Hoechst 33258 dyeing, we found that the typical apoptosis morphology had changed. Secretion of IL-6 in the serum decreased significantly (P < 0.05), and STAT3 levels were reduced. RPTS can significantly promote apoptosis in SW480 colorectal cancer cells. The mechanism may be that it suppresses the secretion of IL-6 and inhibits the IL-6/JAK-STAT3 protein signaling pathway.

Design, synthesis and anticonvulsant activity evaluation of novel 4-(4-substitutedphenyl)-3-methyl-1H-1,2,4-triazol-5(4H)-ones.

A series of novel 4-(4-substitutedphenyl)-3-methyl-1H-1,2,4-triazol-5(4H)-one derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock test (MES) and their neurotoxicity was evaluated by the rotarod neurotoxicity test (TOX). In the MES test, compound 4-{4-[(3-fluorobenzyl)oxy]phenyl}-3-methyl-1H-1,2,4-triazol-5(4H)-one (4n) was found to possess better anticonvulsant activity and higher safety than marketed drugs Carbamazepine with an ED50 value of 25.5 mg/kg and protective index (PI) value>48.8. In addition, the potency of compound 4n against seizures induced by Pentylenetetrazole, 3-Mercaptopropionic acid, and Bicuculline suggested its broad spectrum activity, and the mechanisms of action including inhibition of voltage-gated ion channels and modulation of GABAergic activity might involve in its anticonvulsant activity.

Fusarium solani and Fusarium oxysporum Associated with Root Rot of Glycyrrhiza uralensis in China.

Liquorice (root of Glycyrrhiza uralensis Fisch.) is an important Chinese traditional medicine for many ailments (4). From 2002, severe outbreaks of root rot occurring on cultivated G. uralensis plants in Ningxia, China, have affected the yield and quality of liquorice and been considered as a major threat to commercial production of liquorice. Approximately 30% of the plants die from this disease in Ningxia every year. The disease, mainly affecting 2- to 4-year-old G. uralensis seedlings, begins with brown rot of root tips or lateral roots followed by internal decay of taproots during June to August every year. The infected plants are wilted with chlorotic foliage and easily pulled up from the soil. Root rot is clearly visible as a severe brown discoloration of vascular tissue along taproots. In severe cases, white mycelia are clearly visible on the surface of diseased roots and roots are decomposed. Isolations from diseased roots were made on potato dextrose agar (PDA) amended with streptomycin sulfate. Isolates (n = 78) were recovered from symptomatic roots (n = 105) and pure cultures were established by the single spore method. The two most frequently isolated fungi were transferred to potato sucrose agar and identified as Fusarium solani (61.5%) and F. oxysporum (30.8%) (1). The monophialides bearing microconidia of F. solani are long when compared to those of F. oxysporum. Genomic DNA of strains F. solani G013 and F. oxysporum FLR were extracted from mycelia with the cetyltrimethylammonium bromide (CTAB) method. Primers EF1-728F and EF1-986R were used to amplify the translation elongation factor-1α (TEF-1α) gene (2). The TEF-1α sequences of F. solani G013 (GenBank Accession No. AB777258) and F. oxysporum FLR (AB777257) shared 99 and 100% similarity with F. solani isolate NRRL52790 and F. oxysporum isolate NRRL 38328, respectively. Pathogenicity tests with one representative isolate of each species were conducted in the greenhouse on 1-month-old potted G. uralensis seedlings (12 plants per treatment). Isolates of the tested fungi were transferred to PDA and incubated in darkness at 24 ± 1°C for 7 days. Plant taproots about 5 cm below the soil surface were wounded with a sterile needle and five 5-mm-diameter fungal disks on the margin of colony were taken and firmly placed on the wounded location of each taproot with tinfoil; wounded taproots of seedlings inoculated with sterile PDA disks were used as controls (3). Root rot was assessed 2 months after inoculation. F. solani G013 and F. oxysporum FLR produced root rot symptoms on inoculated plants that were the same as those observed in field plants, and the fungi were reisolated from roots with typical symptoms. Control plants inoculated with sterile PDA disks remained asymptomatic, and no pathogen was isolated from them. To our knowledge, this is the first report of root rot caused by F. solani and F. oxysporum on G. uralensis in China. Effective control strategies are needed to minimize losses. References: (1) C. Booth. The Genus Fusarium. Commonwealth Mycological Institute, Farnham Royal, 1971. (2) I. Carbone and L. M. Kohn. Mycologia 91:553, 1999. (3) M. Guo et al. Plant Dis. 96:909, 2012. (4) T. Wu et al. Am. Assoc. Pharm. Sci. J. 13:1, 2011.

Promoting adult hippocampal neurogenesis: a novel strategy for antidepressant drug screening.

Major depression is a common mood disorder that affects overall health; currently, almost all of the available antidepressants have the same core mechanisms of action through promotion of serotonin or noradrenaline function in the brain. The major limitation of today's antidepressants is that chronic treatment (3 - 6 weeks) is required before a therapeutic benefit is achieved. More effective and faster treatments for depression are needed. Adult neurogenesis is the birth of new neurons, which continues postnatally and into adulthood in the brains of multiple species, including humans. Recently, a large body of evidence gives rise to the hypothesis that the antidepressant effect and increases in adult hippocampal neurogenesis may be causally related. Multiple classes of antidepressants increase hippocampal neurogenesis in a chronic, but not acute, time course. This effect corresponds to the therapeutic time lag associated with current antidepressants. In addition, antidepressants are not effective in behavioral models of depression when hippocampal neurogenesis is prevented. This review examines the current understanding of adult neurogenesis and the evidence of the causal relationship between antidepressant effects and adult hippocampal neurogenesis. We also present our recent research findings, which support a promising strategy for enhancing adult hippocampal neurogenesis that might be a new approach for the development of novel antidepressants.

Glyceraldehyde-3-phosphate dehydrogenase: activity inhibition and protein overexpression in rotenone models for Parkinson's disease.

Rotenone, a widely used pesticide and an environmental risk factor for Parkinson's disease (PD), induces nigrostriatal injury, Lewy body-like inclusions, and Parkinsonian symptoms in rat models for PD. Our previous data indicated that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) overexpression and glycolytic inhibition were co-current in rotenone-induced PC12 (rat adrenal pheochromocytoma cells) cell death. However, whether GAPDH overexpression plays any role in dopaminergic neurodegeneration in vivo remains unknown. In this study, we have found that GAPDH overexpression and GAPDH-positive Lewy body-like aggregates in nigral dopaminergic neurons while nigral GAPDH glycolytic activity decreases in rotenone-based PD animal models. Furthermore, GAPDH knockdown reduces rotenone toxicity significantly in PC12. These in vitro and in vivo data suggest that GAPDH contributes to the pathogenesis of Parkinson's disease, possibly representing a new molecular target for neuroprotective strategies and alternative therapies for PD.

Clioquinol and vitamin B12 (cobalamin) synergistically rescue the lead-induced impairments of synaptic plasticity in hippocampal dentate gyrus area of the anesthetized rats in vivo.

Lead (Pb(2+)) exposure in development induces impairments of synaptic plasticity in the hippocampal dentate gyrus (DG) area of the anesthetized rats in vivo. The common chelating agents have many adverse effects and are incapable of alleviating lead-induced neurotoxicity. Recently, CQ, clioquinol (5-chloro-7-iodo-8-hydroxy-quinoline), which is a transition metal ion chelator and/or ionophore with low affinity for metal ions, has yielded some promising results in animal models and clinical trials related to dysfunctions of metal ions. In addition, CQ-associated side effects are believed to be overcome with vitamin B12 (VB12) supplementation. To determine whether CQ treatment could rescue impairments of synaptic plasticity induced by chronic Pb(2+) exposure, we investigated the input/output functions (I/Os), paired-pulse reactions (PPRs) and long-term potentiation (LTP) of different treatment groups in hippocampal DG area of the anesthetized rat in vivo by recording field potentials and measured hippocampal Pb(2+) concentrations of different treatment groups by PlasmaQuad 3 inductive coupled plasma mass spectroscopy. The results show: CQ alone does not rescue the lead-induced impairments of synaptic plasticity in hippocampal DG area of the anesthetized rats in vivo; VB12 alone partly rescues the lead-induced impairments of LTP; however the co-administration of CQ and VB12 totally rescues these impairments of synaptic plasticity and moreover, the effects of CQ and VB12 co-administration are specific to the lead-exposed animals.

Experimental study on sludge reduction by ultrasound.

In recent years, considerable impetus emerges to develop strategies for reducing excess sludge produced in biological wastewater treatment (BWT) systems. In this study, an experiment on sludge reduction by ultrasound treatment was conducted. The influences of sonication on observed yield, sludge reduction, effluent quality, sludge settleability and stability were extensively evaluated. It was found that ultrasound had an impressive potential to reduce sludge production. Moreover, it was also concluded that a treatment time of 10 minutes was more cost-effective for sludge reduction, and a reduction by 44% was reached with an ultrasonic intensity of 0.25 w/ml. The reduction could be mainly attributed to disintegration of bio-flocs and cryptic growth. In addition, sonication time seemed to be more effective to reduce sludge production compared with ultrasonic intensity. Slight deterioration of the effluent quality and some variations of the sludge settleability and stability were observed after ultrasound treatment.

Cloning and characterization of a novel zinc finger protein (MDZF) that is associated with monocytic differentiation of acute promyelocytic leukemia cells.

AIM: To study the characteristics of a novel zinc finger protein designated as monocytic differentiation-associated zinc finger protein (MDZF) and its role in the differentiation of leukemia cells. METHODS: The mRNA expression of MDZF in tissues and cells was analyzed by Northern blot and RT-PCR. Polyclonal antibodies against the N terminus of MDZF were used to analyze protein expression in hematopoietic cell lines and subcellular location of MDZF in promyelocytic NB4 cells. The NB4 cells treated with TPA or ATRA at different intervals were harvested and then the expression level of MDZF protein was determined by Western blot. RESULT: A full-length cDNA was successfully identified from a human monocyte-derived dendritic cell cDNA library which encodes 610 amino acids with eight C2H2 zinc finger motifs and one POZ domain. It was located on chromosome 3 according to the genome database. This novel zinc finger protein was designated as MDZF. One transcript isoform of MDZF was also cloned by RT-PCR. Northern blot showed that MDZF mRNA was restrictedly expressed in heart, skeleton muscle, kidney, liver, and placenta. MDZF protein was expressed in all hematopoietic cell lines examined. Immunoblotting and confocal analysis indicated a dominant cytoplasmic location of MDZF in NB4 cells. Furthermore, after NB4 cells were treated with TPA for 48 h and differentiated into monocytes, MDZF expression increased fivefold in the NB4 cells, but no effect was observed in NB4 cells treated with ATRA. CONCLUSION: A novel zinc finger protein MDZF was cloned. MDZF is upregulated in monocytic, but not granulocytic, differentiation of NB4 acute promyelocytic leukemia cells. MDZF may be a candidate regulator of monocytic differentiation.

Effects of electroacupuncture on blood-brain barrier after cerebral ischemia-reperfusion in rat.

The effect of electroacupuncture (EA) on the blood-brain barrier (BBB) after cerebral ischemia-reperfusion (I-R) was investigated in rats. The dye Evans Blue (EB) was used as a tracer for assessing the disruption of BBB. Fluorescence quantification of EB was performed to explore the temporal pattern of permeability of BBB after the cerebral I-R with a fluorescence spectrophotometer (HITACHI 650-60). Furthermore, the morphology of BBB opening was detected under confocal laser scanning microscopy system. It was found that the BBB opening after cerebral I-R was biphasic. A rare scattered extravasation of EB was detected 2 hours after cerebral I-R. The EB extravasation reached its first peak at 6 h then decreased at 24 h and increased again at the time-point of 48h after cerebral I-R. EA can attenuate the disruption of BBB after cerebral I-R. EA could not only limit the area of extravasation of EB, but also reduce the concentration of extravasation of EB in the rat brain after cerebral I-R. The results indicated that one of the mechanisms of curative effect of EA on the cerebral ischemia might be due to its function of protecting the integrity of BBB.

Alteration of orphanin FQ immunoreactivity and ppOFQ mRNA by combination of melatonin with electroacupuncture.

The aim of the present study was to observe the alternation of central orphanin FQ (OFQ, also known as nociceptin) system while electroacupuncture (EA) combined with melatonin (MEL). The experiments were carried out to investigate the changes of OFQ-like immunoreactivity and prepro-orphanin FQ (ppOFQ) mRNA in some certain nuclei of the rat brain. Using immunohistochemical technique we found that the level of OFQ-like immunoreactivity was increased significantly in some pain-modulation-related nuclei, such as ventromedial hypothalamic nucleus, raphe magnus nucleus, dorsal raphe nucleus and periaqueductal gray (PAG) after intraperitoneal (i.p.) injection of MEL 60 mg/kg, and it was further enhanced while MEL combined with EA. By using in situ hybridization, we found that ppOFQ mRNA expression was decreased in the same nuclei after the administration of MEL, and further decreased following the combination of EA and MEL. The results suggested that attenuating the release and synthesis of OFQ in the brain is one of the mechanisms that melatonin promotes acupuncture analgesia.