[Short-term complications after transanal total mesorectal excision for mid-low rectal cancer].

Objective: To summarize short-term postoperative complications of transanal total mesorectal excision (taTME) in the treatment of middle-low rectal cancer. Methods: A descriptive case series of cases was constructed. Clinical data of consecutive 83 patients with mid-low rectal cancer who received taTME treatment from November 2016 to April 2021 at Department of General Surgery of Beijing Friendship Hospital, Capital Medical University were collected. Among 83 patients, 58 (69.9%) were males, with a mean age of (61.4±11.8) years; 42 (50.6%) were low rectal cancer, 41 (49.4%) were middle rectal cancer. Short-term postoperative complication was defined as complication occurring within 30 days after operation. The complication was graded according to the Clavien-Dindo classification. At the same time, the morbidity of short-term postoperative complication in the first 40 patients and that in the last 43 patients were compared to understand the differences before and after passing the taTME learning curve. Results: Two patients (2.5%) were converted to laparotomy ; 78 (94.0%) completed anastomosis.While 5 (6.0%) underwent permanent stoma. The total operation time of transabdominal+ transanal procedure was (246.9±85.0) minutes, and the median intraoperative blood loss was 100 (IQR: 100) ml. Seventy-five cases (75 /78, 96.2%) underwent defunctioning stoma, including 74 cases of diverting ileostomy, 1 case of diverting transverse colostomy and 3 cases without stoma. The morbidity of complication within 30 days after operation was 38.6% (32/83), and the morbidity of complication after discharge was 8.4% (7/83). Minor complications accounted for 31.3% (26/83) and major complications accounted for 7.2% (6/83). No patient died within 30 days after operation. The incidence of anastomotic leakage was 15.4% (12/78). Eight patients (9.6%) were hospitalized again due to complications after discharge. The median postoperative hospital stay was 7 (IQR: 3) days. All the patients with minor (I-II) complications received conservative treatment. One patient with grade C anastomotic leakage was transferred to intensive care unit and received a second operation due to sepsis and multiple organ dysfunction. Two patients with paralytic ileus (Clavien-Dindo IIIa) underwent endoscopic ileus catheter placement. There were 3 patients with Clavien-Dindo III or above respiratory complications, including 1 patient with pleural effusion and ultrasound-guided puncture, 2 patients with respiratory failure who were improved and discharged after anti-infection and symptomatic treatment. One patient underwent emergency ureteral stent implantation due to urinary infection (Clavien-Dindo IIIb). The morbidity of postoperative complication in the first 40 cases was 50.0% (20/40), and that in the latter 43 cases decreased significantly (27.9%, 12/43), whose difference was statistically significant (χ(2)=4.270, P=0.039). Conclusions: The procedure of taTME has an acceptable morbidity of short-term postoperative complication in the treatment of mid-low rectal cancer. The accumulation of surgical experience plays an important role in reducing the morbidity of postoperative complication.

LINC00106 prevents against metastasis of thyroid cancer by inhibiting epithelial-mesenchymal transition.

OBJECTIVE: Thyroid cancer (TC) is a common malignant tumor of the endocrine system, and its morbidity and mortality are in the high places. Recent studies have focused on exploring biological markers and targeted therapy for TC. This research aims to elucidate the role of LINC00106 in the progression of TC and the regulatory mechanisms. PATIENTS AND METHODS: Differential level of LINC00106 in a downloaded profile containing TC and normal tissues from GEPIA database was analyzed. Subsequently, its level in TC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between LINC00106 level and clinical data of TC patients was assessed, including age, tumor staging, lymphatic metastasis, and overall survival. After transfection of si-LINC00106, TC cell metastasis was evaluated by wound healing and transwell assay. Relative levels of E-cadherin, N-cadherin, ß-catenin, and Vimentin regulated by LINC00106 were determined using qRT-PCR and Western blot. RESULTS: LINC00106 was downregulated in TC tissues than normal ones. Its level was correlated to tumor staging, lymphatic metastasis and overall survival in TC patients. The knockdown of LINC00106 in BCPCP and TPC-1 cells enhanced migratory and invasive abilities and triggered the process of epithelial-mesenchymal transition (EMT). CONCLUSIONS: LINC00106 is lowly expressed in TC specimens, which attenuates migratory and invasive abilities in TC by inhibiting EMT as a tumor suppressor.

Effect of air pollution on hospital admissions for systemic lupus erythematosus in Bengbu, China: a time series study.

Recently, exposure to air pollutants has been associated with the development and progression of systemic lupus erythematosus (SLE). The current study aims to evaluate the effects of air pollutants on SLE hospital admissions in Bengbu, China. We performed distributed lag non-linear model combined with quasi-Poisson generalized linear regression to assess the impacts of air pollutants on SLE admissions from 2015 to 2017. Subgroup analyses by admission status (first admission or readmission) were also evaluated. A total of 546 hospital admissions during 2015-2017 were included. For single-day lag structures, the risk effects occurred from lag 2 to lag 9 for the 75th percentile particulate matter (PM)2.5, lag 3 to lag 9 for the 80th percentile PM2.5. For cumulative lag structures, the risk effects occurred from lag 0-5 to lag 0-14 for both 75th PM2.5 and 80th PM2.5, and no significant effect was observed for 90th PM2.5. In addition, the adverse effects on SLE first admissions occurred from lag 0 to lag 1 for NO2, lag 1 to lag 2 for SO2. The maximum effect of PM2.5 on SLE was 4.27 (95% confidence interval: 1.34-13.59) at lag 0-13 day, the minimum effect value was 1.12 (95% confidence interval: 1.03-1.23) at lag 9 day. These findings demonstrate that high PM2.5, NO2 and SO2 are associated with SLE hospital admissions. In addition, this study further revealed that exposure to high concentration of PM2.5 increased the risk of SLE relapse, while high levels of NO2 and SO2 increased the risk of SLE first admissions.

Global public interest in systemic lupus erythematosus: an investigation based on internet search data.

OBJECTIVE: This study aims at investigating the global public interest in seeking information about systemic lupus erythematosus (SLE) using Google Trends (GT). METHODS: An electronic search was performed using GT with the search term lupus as well as the option of disease from January 2004 to December 2018. Cosinor analysis was applied to detect the seasonality of SLE-related relative search volume (RSV). In addition, analysis on SLE-related topics including "hot topics" and "top rising topics" was also conducted. RESULTS: Overall, SLE-related RSV showed a decreasing trend from January 2004 to December 2013 and then demonstrated a slowly increasing trend from January 2014 to December 2018. Cosinor test showed no significant seasonal variation in SLE-related RSV (p > .025). RSV peaked in May and reached the trough in November. The top seven rising topics were Selena Gomez, Sjögren syndrome, autoimmunity, rheumatoid arthritis, rheumatology, antinuclear antibody and autoimmune disease. CONCLUSION: The results from GT analysis showed slowly increasing internet searches for SLE in recent years. This trend was followed by a peak of RSV in May and reached its lowest level in November. However, globally, the results did not reveal a significant seasonal variation in GT for SLE. Additionally, the top fast-growing topics regarding SLE may be valuable for doctors and nurses to provide timely education of the disease to patients, as well as promote the development of public health.

Elevated serum levels of interleukin-1ß and interleukin-33 in patients with systemic sclerosis in Chinese population.

PURPOSE OF THE STUDY: Systemic sclerosis (SSc) is a multisystem autoimmune disease. Although the pathogenesis of the disease remains incompletely understood, some cytokines or growth factors which regulate SSc induction may be involved in the injury of endothelial cells and the modulation of leukocyte function. We aimed to perform this case-control study to determine serum levels of interleukin (IL)-1α, IL-1ß, IL-18 and IL-33 and their associations with clinical manifestations in SSc patients. MATERIALS AND METHODS: There were 56 patients with SSc and 56 healthy individuals who were recruited from local hospital between 2012 and 2014. Serum IL-1α, IL-1ß, IL-18 and IL-33 levels were measured with specific enzyme-linked immunosorbent assay kits. RESULTS: Univariate analysis revealed that serum IL-1ß, IL-18 and IL-33 levels in SSc patients were significantly higher than that in healthy controls. After adjusting possible confounding factors (sex, age, smoking and drinking) by multivariable analyses, serum IL-1ß levels (OR = 1.082; 95 % CI: 1.013-1.155) and serum IL-33 levels (OR = 1.100; 95 %CI: 1.022-1.185) were still related factors. There were interrelationships among the serum levels of IL-1α, IL-1ß, IL-18 and IL-33 and these associations were not consistent in SSc patients and controls. No associations of serum IL-1α, IL-1ß, IL-18 and IL-33 levels with clinical parameters were found. CONCLUSION: IL-1ß and IL-33 may contribute to the development of SSc. While there were no direct associations between these cytokines and disease manifestations, they still could be considered as serum markers of development of SSc. Further studies are required to validate this incipient data.

[Screening for precursors of colorectal cancer].

Screening has been proven to be effective for the control of colorectal cancer (CRC). The target of CRC screening is shifting from CRC to colorectal neoplasia (CN), the precursors of CRC. Based on the the latest national guideline, the Consensus of Screening for CRC and CN, and the recent research of precursors both at home and abroad. This paper summarizes the progress in the research of risk factors, risk prediction model, screening strategy optimization, colonoscopy quality control, sessile serrated adenoma identification and follow up as well as the recognition of precursors.

[Clinical significance of lymphatic metastasis between sternocleidomastoid and sternohyoid muscle in papillary thyroid cancer].

Objective: To explore the clinical significance of metastasis of lymph nodes between sternocleidomastoid and sternohyoid muscle (LNSS) in papillary thyroid cancer (PTC). Methods: A total of 175 patients with PTC who underwent thyroidectomy with LNSS dissection were retrospectively analyzed. Univariate and multivariate Logistic regression analyses were used to determine the independent risk factors for LNSS metastasis in PTC. Results: The rate of detectable LNSS was 70.9% (124/175) and metastasis rate was 7.4% (13/175). Of 13 cases with LNSS metastasis, 10 with the coexistence of cervical lymph node metastasis. Univariate Logistic regression analysis showed that multiple focal cancer, tumor located in the lower pole of thyroid, belt-shaped muscle invasion, lateral cervical lymph node metastasis, cN+ , the number of cervical lymph nodes with metastasis and the number of lymph nodes with metastasis in level Ⅳwere the risk factors for LNSS metastasis (P<0.05). Multivariate Logistic regression analysis suggested that tumor located in the lower pole of thyroid and the number of cervical lymph nodes with metastasis >6 were the independent risk factors for LNSS metastasis (P<0.05). Given the number of cervical lymph nodes with metastasis as a predictor for the LNSS metastasis, the sensitivity was 92.3%, the specificity was 66.7% and the accuracy rate was 68.6%. Conclusions: LNSS metastasis is commom in PTC, with a metastasis rate of 7.4%. PTC in the lower pole of thyroid and the number of cervical lymph nodes with metastasis > 6 are independent risks for LNSS metastasis.

Association of thymidylate synthase polymorphisms with the tumor response to preoperative chemoradiotherapy in rectal cancer: a systematic review and meta-analysis.

Preoperative chemoradiotherapy (pCRT) followed by surgery is currently the standard therapy for patients with locally advanced rectal cancer. It is very important to develop biomarkers to prior identify the patients who have a higher likelihood of responding to pCRT. Recently, a series of studies have been conducted to investigate the association of thymidylate synthase (TYMS) polymorphisms with the tumor response to pCRT in rectal cancer, but the results were not consistent and conclusive. In the present study, we performed a systematic literature search for relevant studies up to 30 March 2015 and conducted a meta-analysis to summarize and clarify the association between the TYMS polymorphisms and the tumor response to pCRT in rectal cancer. Finally, 7 studies containing 892 cases for TYMS 2R/3R polymorphism, 7 studies involving 715 cases for TYMS 1494del6 polymorphism and 6 studies containing 616 cases for TYMS 5' untranslated region (UTR) expression allele polymorphism were analyzed in the meta-analysis. The results suggested that TYMS 2R/3R was associated with the response and the patients with 2R/2R or 2R/3R genotype with rectal cancer might benefit more from pCRT than others. On the contrary, neither 1494del6 nor 5'UTR expression allele polymorphisms was associated with the response to pCRT.

[The clinical significance of Delphian lymph node metastasis in papillary thyroid cancer].

Objective: To evaluate the clinical significance of Delphian lymph node (DLN) metastasis in papillary thyroid cancer (PTC). Method: A total of 505 cases with PTC confirmed pathologically in our hospital between January 2015 and December 2015 were retrospectively reviewed. 208 patients with DLN assessed separately by histopathologic examination who underwent primary surgery for PTC were included for the following analysis. Results: In 208 patients, the detection rate of DLN was 63.0% and the metastasis rate of DLN was 21.4%. DLN metastasis was correlated with PTC multifocality (P=0.038), tumor size over 1cm (P=0.001), BRAFV600E mutation (P=0.017) and central neck node metastasis (P<0.001). Tumor size over 1cm (95%CI 1.308-9.909, OR=3.600, P=0.013) and the number of node with central neck metastasis (95%CI 1.313-2.163, OR=1.685, P<0.001) were independent risk factors for DLN metastasis. The presence of DLN metastasis was associated with an 8.8-fold higher frequency of central neck node metastasis compared to cases without DLN metastasis. Among patients with DLN metastases, central lymph node metastasis was more common in the cases with lateral neck node metastases compared to those without lateral neck node metastases (6.5±3.0 vs 1.5±0.7, P=0.009), and 5 of the 6 patients also presented with PTC multifocality and BRAFV600E mutation. Conclusion: DLN metastasis implies a higher possibility of central neck lymph node metastasis. DLN should be assessed during operation to provide information for neck dissection, post-operative administration and follow-up strategy.

Elevated plasma interleukin-37 levels in systemic lupus erythematosus patients.

This study aims to evaluate the plasma interleukin (IL)-37 levels in systemic lupus erythematosus (SLE) patients, as well as its association with major clinical and laboratory features. Ninety consecutively selected SLE patients and 78 community-based healthy controls were recruited. Plasma IL-37 levels were detected by enzyme-linked immunosorbent assay (ELISA). The major clinical and laboratory data of SLE patients were also recorded. The results showed that IL-37 level was significantly higher in the plasma of patients with SLE compared with controls (p = 0.028). The correlation of plasma IL-37 levels with major clinical and laboratory data of SLE patients was also analyzed, and the results showed that anti-Sm and anti-RNP were negatively associated with plasma IL-37 levels of SLE patients, while C3 was positively associated with plasma IL-37 levels of SLE patients. No significant associations of IL-37 with other clinical and laboratory parameters were observed (all p > 0.05). In conclusion, elevated plasma IL-37 level and its associations with anti-Sm, anti-RNP and C3 in SLE patients suggest that IL-37 may be implicated in this disease.

Aspirin-triggered Lipoxin A4 attenuates mechanical allodynia in association with inhibiting spinal JAK2/STAT3 signaling in neuropathic pain in rats.

Aspirin-triggered Lipoxin A4 (ATL), as a Lipoxin A4 (LXA4) epimer, is endogenously produced by aspirin-acetylated cycloxygenase-2 (COX-2) and plays a vital role in endogenous anti-inflammation via the LXA4 receptor (ALX). Recent investigations have indicated that spinal neuroinflammation and the activation of the Janus Kinase 2 (JAK2)/Signal Transducers and Transcription Activators 3 (STAT3) signaling pathway are involved in neuropathic pain states. However, the effect of ATL on neuroinflammation and JAK2/STAT3 signaling in chronic constriction injury (CCI)-induced neuropathic pain in rats has not been well-studied. The present study demonstrated the anti-inflammatory and analgesic effect of ATL on neuropathic pain and assessed the role of spinal JAK2/STAT3 signaling on the effect of ATL. Intrathecal administration of ATL significantly attenuated mechanical allodynia via spinal ALX and inhibited the upregulation of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) on day 7 of CCI surgery. In addition, ATL markedly suppressed the upregulation of p-STAT3 induced by the neuropathic pain. Blockade of JAK2-STAT3 signaling with intrathecal administration of the JAK2 inhibitor AG490 or the STAT3 inhibitor S3I-201 clearly reduced mechanical allodynia and the upregulation of pro-inflammatory cytokines in CCI rats. Interestingly, inhibition of JAK2/STAT3 signaling via ATL or the specific signaling inhibitor (AG49, S3I-201) further promoted the increased expression of suppressor of cytokine signaling 3 (SOCS3) mRNA in the spinal cord induced by CCI surgery. Taken together, our results suggested that the analgesic effect of ATL was mediated by inhibiting spinal JAK2/STAT3 signaling and hence the spinal neuroinflammation in CCI rats.

Involvement of the spinal NALP1 inflammasome in neuropathic pain and aspirin-triggered-15-epi-lipoxin A4 induced analgesia.

Neuroinflammation plays an important role in nerve-injury-induced neuropathic pain, but the explicit molecular mechanisms of neuroinflammation in neuropathic pain remain unclear. As one of the most critical inflammatory cytokines, interleukin-1ß (IL-1ß) has been regarded as broadly involved in the pathology of neuropathic pain. The inflammasome caspase-1 platform is one primary mechanism responsible for the maturation of IL-1ß. Lipoxins, a type of endogenous anti-inflammatory lipid, have proved to be effective in relieving neuropathic pain behaviors. The present study was designed to examine whether the inflammasome caspase-1 IL-1ß platform is involved in chronic constriction injury (CCI)-induced neuropathic pain and in lipoxin-induced analgesia. After rats were subjected to the CCI surgery, mature IL-1ß was significantly increased in the ipsilateral spinal cord, and the inflammasome platform consisting of NALP1 (NAcht leucine-rich-repeat protein 1), caspase-1 and ASC (apoptosis-associated speck-like protein containing a caspase-activating recruitment domain) was also activated in spinal astrocytes and neurons, especially at the superficial laminae of the spinal dorsal horn; The aspirin-triggered-15-epi-lipoxin A4 (ATL), which shares the potent actions of the endogenous lipoxins, was administered to the CCI rats. Repeated intrathecal injection with ATL markedly attenuated the CCI-induced thermal hyperalgesia and significantly inhibited NALP1 inflammasome activation, caspase-1 cleavage, and IL-1ß maturation. These results suggested that spinal NALP1 inflammasome was involved in the CCI-induced neuropathic pain and that the analgesic effect of ATL was associated with suppressing NALP1 inflammasome activation.

Huperzine A inhibits CCL2 production in experimental autoimmune encephalomyelitis mice and in cultured astrocyte.

The active role of chemokines and inflammatory cytokines in the central nervous system (CNS) during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been clearly established. Recent studies from our laboratory reported that Huperzine A (HupA) can attenuate the disease process in EAE by the inhibition of inflammation, demyelination, and axonal injury in the spinal cord as well as encephalomyelitic T-cell proliferation. In this study, the effects of low dose HupA on CCL2, TNF-alpha, IL-6, and IL-1beta expression were evaluated in EAE. The effect of HupA on lipopolysachharide (LPS)-induced inflammatory molecule secretion was investigated in cultured-astrocytes in vitro. In MOG35-55-induced EAE mice, intraperitoneal injections of HupA (0.1 mg/kg•d−1) significantly suppressed the expression of CCL2, IL-6, TNF-alpha, and IL-1beta in the spinal cord. HupA also repressed LPS-induced CCL2 production, but with little influence on pro-inflammatory cytokines in primary cultured astrocytes. The inhibition effect of HupA on CCL2 is PPARgamma-dependent and nicotine receptor-independent. Conditioned culture media from HupA-treated astrocyte decreased PBMC migration in vitro. Collectively, these results suggest that HupA can ameliorate EAE by inhibiting CCL2 production in astrocyte, which may consequently decrease inflammatory cell infiltration in the spinal cord. HupA may have a potential therapeutic value for the treatment of MS and other neuroinflammatory diseases.

Spinal interleukin-33 and its receptor ST2 contribute to bone cancer-induced pain in mice.

Cancer pain, particularly bone cancer pain, affects the quality of life of cancer patients, and current treatments are limited. Interleukin (IL)-33, a new member of the IL-1 super family, has been reported to be involved in the modulation of inflammatory pain. However, studies focused on its role in the modulation of cancer pain have been rare. The present study was designed to investigate whether spinal IL-33/ST2 signaling was involved in bone cancer-induced pain in mice. Bone cancer was induced via intra-femoral inoculation of 4T1 mammary carcinoma cells. The mice inoculated with carcinoma cells showed mechanical allodynia, heat hyperalgesia and a reduction in limb use, whereas phosphate-buffered saline or heat-killed cells-injected mice showed no significant difference compared to non-treated mice. The pain hypersensitive behaviors worsened over time and with bone destruction. Both the mRNA and the protein levels of IL-33 and relative cytokines (IL-1ß, IL-6, TNF-a) were significantly increased in the spinal cord after the inoculation of carcinoma cells. Intrathecal administration of ST2 antibody to block IL-33/ST2 signaling alleviated pain behaviors in a dose-dependent manner in bone cancer pain mice compared with vehicle-injected mice. Moreover, the ST2(-/-) mice showed a significant amelioration of limb use and heat hyperalgesia compared to wild-type mice. Meanwhile, concentrations of spinal IL-1ß, IL-6 and TNF-a in the cancer-bearing ST2(-/-) mice had no significant changes. These data further suggested that IL-33/ST2 signaling played a vital role in cancer pain. Our results provided evidence that IL-33 and its receptor ST2 may be a potential therapeutic target for the treatment of pain in bone cancer patients.

Interleukin-33 mediates formalin-induced inflammatory pain in mice.

Interleukin-33 (IL-33), a member of the IL-1 family, has attracted growing interest since its discovery in 2003. IL-33 has been implicated in many diseases, including arthritis, asthma, allergies, and cardiovascular and infectious diseases. However, few studies have investigated its role in the transmission and modulation of pain. The present study was designed to explore the possible roles of IL-33 and its receptor, ST2, in formalin-induced inflammatory pain in mice. We found that both subcutaneous (s.c., 300 ng) and intrathecal injection (i.t., 3 ng) of recombinant IL-33 (rIL-33) increased paw lifting and licking time not only in normal mice but also in formalin models. Administration of ST2 antibody, which blocked the IL-33/ST2 signaling, alleviated the formalin-induced spontaneous pain behavior. Moreover, the ST2(-/-) mice showed significantly decreased pain behavior, as well as reduced ultrasonic vocalization induced by formalin, compared with the wild-type group. Additionally, ST2 antibody alleviated the potentiating effects of rIL-33 on pain behavior in the formalin mice, indicating that IL-33 plays a role in pain modulation through its ST2 receptor. These data suggest IL-33 and its ST2 receptor mediate formalin-induced inflammatory pain, and as a result this cytokine and its receptor may be new targets for the development of analgesics.

Extracellular signal-regulated kinase activation in spinal astrocytes and microglia contributes to cancer-induced bone pain in rats.

Cancer pain, especially cancer-induced bone pain, affects the quality of life of cancer patients, and current treatments for this pain are limited. The present study demonstrates that spinal extracellular signal-regulated kinase (ERK) activation in glial cells plays a crucial role in cancer-induced bone pain. From day 4 to day 21 after the intra-tibia inoculation with Walker 256 mammary gland carcinoma cells, significant mechanical allodynia was observed as indicated by the decrease of mechanical withdrawal thresholds in the von Frey hair test. Intra-tibia inoculation with carcinoma cells induced a vast and persistent (>21 D) activation of ERK in the bilateral L2-L3 and L4-L5 spinal dorsal horn. The increased pERK1/2-immunoreactivity was observed in both Iba-1-expressing microglia and GFAP-expressing astrocytes but not in NeuN-expressing neurons. A single intrathecal injection of the selective MEK (ERK kinase) inhibitors PD98059 (10 µg) on day 12 and U0126 (1.25 and 3 µg) on day 14, attenuated the bilateral mechanical allodynia in the von Frey hair test. Altogether, our results suggest that ERK activation in spinal microglia and astrocytes is correlated with the onset of allodynia and is important for allodynia maintenance in the cancer pain model. This study indicated that inhibition of the ERK pathway may provide a new therapy for cancer-induced bone pain.

Saikosaponins: a potential treatment option for systemic lupus erythematosus.

While the exact cause of systemic lupus erythematosus (SLE) is still unknown, modern medicine has a number of effective treatments for this complex disorder. Corticosteroid hormones help reduce inflammation, antimalarial treatments address flare-ups and immunosuppressive medications work to keep the immune system in check. All these therapies are well tolerated, but accompany an increased risk of infection and nephrotoxicity. Recently, several studies showed that a number of natural and herbal products may also help some SLE patients deal with the debilitating symptoms. In this brief report, we proposed a traditional Chinese medicinal herb--Saikosaponins, and discussed its potential as a treatment option for SLE.

Repeated clomipramine treatment reversed the inhibition of cell proliferation in adult hippocampus induced by chronic unpredictable stress.

Adult hippocampal neurogenesis has been demonstrated in several species and is regulated by both environmental and pharmacological stimuli. Repeated exposure to stress is known to induce the reduction of neurogenesis in the dentate gyrus (DG) of hippocampus. The present study aimed at determining whether the clinically effective antidepressant clomipramine may influence hippocampal proliferation and neurogenesis in adult rats subjected to the chronic unpredictable stress (CUS) procedure, a model of depression with predictive validity. Repeated administration of clomipramine (5 mg kg(-1), intraperitoneal) for 3 weeks, starting 2 weeks after the beginning of the stress procedure, significantly reversed the reduction of behavior measured by open-field test and forced swimming test. Moreover, rats subjected to stress exhibited a 49.9% reduction of cell proliferation at the end of a 5-week stress period, an effect which was suppressed by clomipramine treatment. These results demonstrated that exposure to CUS, which results in a state of behavioral depression, decreases hippocampal cell proliferation and that these effects can be counteracted by chronic clomipramine treatment.

Developmental expression of key steroidogenic enzymes in the brain of protandrous black porgy fish, Acanthopagrus schlegeli.

In the present study, we tested the hypothesis that the brain of the black porgy fish, Acanthopagrus schlegeli, has the capacity for de novo steroidogenesis and that these neurosteroids may impact sex differentiation. Gonadal histology and Dmrt1 gene expression revealed that the fish were not sex differentiated until 155 dah (days after hatching). We further demonstrated the developmental expressions of the mRNAs encoding for four key neurosteroidogenic enzymes, namely, the cytochrome P450 side chain cleavage (CYP11A1), 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3betaHSD), cytochrome P450c17 (CYP17) and aromatase (CYP19b) in the brain at different post-hatching developmental ages. The results indicated that steroidogenic genes are expressed in brain from the earliest sampling time, 60 dah. Quantitative real-time polymerase chain reaction analysis demonstrated significantly higher expression levels of these enzymes at 120 dah compared to 60 dah in all the brain regions. However, the increase for 3betaHSD was significant only in hypothalamus and midbrain, whereas it was significant only in forebrain and hypothalamus for CYP19b. A decline in mRNA levels were observed for all the genes at 155 dah except in midbrain for CYP11A1 and in hindbrain for CYP19b. Analysis of aromatase enzyme activity showed a significant increase in aromatase activity in the forebrain at 120 dah. Thus, the present study demonstrated for the first time an age- and/or region dependent expression of the mRNAs encoding the steroidogenic enzyme genes in the brain of black porgy. The presence of key steroidogenic enzymes as early as 60 dah, before gonadal sex differentiation, demonstrates that steroid biosynthetic capacity in brain precedes histological gonad differentiation. The mRNA transcripts of these genes showed a synchronous peak at 120 dah, suggesting that oestradiol may be locally formed in most parts of the brain. The study suggests an important role for brain aromatase in male black porgy brain sex differentiation, and considers the possibility of a role for this enzyme in neurogenesis.

Regulation of proinflammatory cytokines gene expression by nociceptin/orphanin FQ in the spinal cord and the cultured astrocytes.

Peripheral inflammation induces central sensitization characterized by the development of allodynia and hyperalgesia to thermal stimuli. Recent evidence suggests that activation of glial cells and a subsequent increase in proinflammatory cytokines contribute to the development of behavioral hypersensitivity after nerve injury or peripheral inflammation. The neuropeptide nociceptin/orphanin FQ (N/OFQ), the endogenous agonist of the N/OFQ peptide receptor (ORL1 receptor), has been demonstrated to play an important role in modulation of nociceptive signals. In the present study, we investigated: (1) astrocyte activation and proinflammatory cytokine expression at the lumbar spinal cord following intraplantar administration of complete Freund's adjuvant (CFA) in rats; (2) the mechanism of N/OFQ on nociception modulation, the relationship between N/OFQ and cytokines in the rat CNS in vivo and in vitro. The results showed: (1) CFA-induced peripheral inflammation evoked robust astrocyte activation and proinflammatory cytokines spinally; (2) down-regulation of cytokine mRNA transcripts by intrathecal administration of N/OFQ, the effects produced by N/OFQ were abolished by combination with ORL1 receptor-specific antagonist [Nphe(1)]N/OFQ(1-13)NH2; (3) ORL1 receptor was expressed on astrocytes of rat spinal cord; (4) cytokine gene expression was inhibited in astrocyte cultures exposed to N/OFQ, the inhibiting effects of N/OFQ were significantly blocked by [Nphe(1)]N/OFQ(1-13)NH2. The present data demonstrated that astrocyte activation and enhanced cytokine expression at the CNS had a role in eliciting behavioral hypersensitivity; the anti-nociception function of N/OFQ might be dependent on cytokines derived from astrocytes, the effects were attributable to the ORL1 receptor pathway.