Inhibition of calcium-sensing receptor by its antagonist promotes gastrointestinal motility in a Parkinson's disease mouse model.

BACKGROUND: The Calcium-sensing receptor (CaSR) participates in the regulation of gastrointestinal (GI) motility under normal conditions and might be involved in the regulation of GI dysmotility in patients with Parkinson's disease (PD). METHODS: CaSR antagonist-NPS-2143 was applied in in vivo and ex vivo experiments to study the effect and underlying mechanisms of CaSR inhibition on GI dysmotility in the MPTP-induced PD mouse model. FINDINGS: Oral intake of NPS-2143 promoted GI motility in PD mice as shown by the increased gastric emptying rate and shortened whole gut transit time together with improved weight and water content in the feces of PD mice, and the lack of influence on normal mice. Meanwhile, the number of cholinergic neurons, the proportion of serotonergic neurons, as well as the levels of acetylcholine and serotonin increased, but the numbers of nitrergic and tyrosine hydroxylase immunoreactive neurons, and the levels of nitric oxide synthase and dopamine decreased in the myenteric plexus in the gastric antrum and colon of PD mice in response to NPS-2143 treatment. Furthermore, the numbers of c-fos positive neurons in the nucleus tractus solitarius (NTS) and cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) increased in NPS-2143 treated PD mice, suggesting the involvement of both the enteric (ENS) and central (CNS) nervous systems. However, ex vivo results showed that NPS-2143 directly inhibited the contractility of antral and colonic strips in PD mice via a non-ENS mediated mechanism. Further studies revealed that NPS-2143 directly inhibited the voltage gated Ca2+ channels, which might, at least in part, explain its direct inhibitory effects on the GI muscle strips. INTERPRETATION: CaSR inhibition by its antagonist ameliorated GI dysmotility in PD mice via coordinated neuronal regulation by both ENS and CNS in vivo, although the direct effects of CaSR inhibition on GI muscle strips were suppressive.

Effects of a self-affirmation intervention among Chinese adolescents during the COVID-19 pandemic: A large-scale randomized controlled trial.

The COVID-19 pandemic, characterized by its highly contagious nature and devastating death toll, posed a dual threat to both physical and psychological well-being. As a potential intervention to alleviate the psychological impact, values-affirmation involves individuals engaging in the activity of writing about their core values. While its effectiveness in non-WEIRD (i.e. Western, Educated, Industrialized, Rich, Democratic) populations, notably among Chinese adults, has been confirmed, it remains largely unexplored whether the intervention can promote mental health in Chinese adolescents, especially in the context of the COVID-19 pandemic. The purpose of this study thus is to provide the first empirical evaluation of this intervention in promoting well-being and alleviating psychological distress among Chinese adolescents during the COVID-19 pandemic. A total of 2,234 students from 112 secondary schools in China were randomly assigned to an affirmation or control condition. The study found that self-affirmation intervention improved students' life satisfaction, mental health, and self-esteem, as well as buffered a decline of their purpose in life; however, no effects were found for clinical measures of depression, anxiety, and loneliness. The results suggest that self-affirmation interventions, while having limited effects on clinically relevant outcomes, can be an effective approach to boost well-being in adolescents during a major crisis, including in a more historically collectivist culture. Implications for self-affirmation theory and cultural psychology, as well as avenues for future research, are discussed.

Activation of calcium-sensing receptors in the basolateral nucleus of the amygdala inhibits food intake and induces anxiety-depressive-like emotions via dopamine system.

The calcium-sensing receptor (CaSR) is abundantly expressed in gastrointestinal mucosa and participates in the regulation of feeding by affecting hormone secretion. Studies have demonstrated that the CaSR is also expressed in feeding-related brain areas, such as the hypothalamus and limbic system, but the effect of the central CaSR on feeding has not been reported. Therefore, the aim of this study was to explore the effect of the CaSR in the basolateral amygdala (BLA) on feeding, and the potential mechanism was also studied. CaSR agonist R568 was microinjected into the BLA of male Kunming mice to investigate the effects of the CaSR on food intake and anxiety-depression-like behaviours. The enzyme-linked immunosorbent assay (ELISA) and fluorescence immunohistochemistry were used to explore the underlying mechanism. Our results showed that microinjection of R568 into the BLA could inhibit both standard and palatable food intake in mice for 0-2 h, induce anxiety-depression-like behaviours, increase glutamate levels in the BLA, and activate dynorphin and gamma-aminobutyric acid neurons through the N-methyl-D-aspartate receptor and thus reduce the content of dopamine in the arcuate nucleus of the hypothalamus (ARC) and ventral tegmental area (VTA), respectively. Our findings suggest that activation of the CaSR in the BLA inhibited food intake and caused anxiety-depression-like emotions. The reduced dopamine levels in the VTA and ARC via glutamatergic signals are involved in these functions of CaSR.

Mindfulness Practice versus Physical Exercise in Enhancing Vitality.

Vitality is important for subjective well-being and performance, which makes strategies for its enhancement an important research issue. While prior research showed that mindfulness practice and physical exercise are both effective at enhancing vitality, no study has compared their efficacy. This study aimed to address this issue. Seventy-one Chinese adults participated in the study and were randomized to one of the intervention groups, i.e., mindfulness practice or physical exercise. The mindfulness practice group completed guided mindfulness trainings, while the physical exercise group completed self-chosen aerobic trainings for seven days. The levels of vitality and its four factors at three time points (baseline, post-intervention, 7-day follow-up) were measured and compared. Compared with physical exercise, mindfulness practice showed stronger effects in enhancing vitality and maintaining the improvements. The findings suggest that guided mindfulness practice is more effective than self-chosen aerobic physical exercise at enhancing vitality and maintaining its improvements.

LncRNA DANCR counteracts premature ovarian insufficiency by regulating the senescence process of granulosa cells through stabilizing the interaction between p53 and hNRNPC.

BACKGROUND: Premature ovarian insufficiency (POI) is one of the common women reproductive endocrine diseases which adversely impacts female fertility, but the etiology and pathogenesis still remain elusive. Recently increasing researches focus on the roles of lncRNA in POI. LncRNA DANCR was involved in cell differentiation and multiple cancers. It's highly expressed in ovary while the role of DANCR in POI is still unknown. RESULTS: Here, we identify a new POI related lncRNA DANCR, which negatively contributes to ovarian granulosa cells aging and follicular atresia. DANCR is proved to be decreasingly expressed in POI patients' granulosa cells. Additionally, Dancr knockout (Dancr-/-) mice were constructed and characterized with POI phenotypes and fertility decline, compared with Dancr+/+ mice. Further, in vitro experiments indicated that DANCR knockdown in granulosa cells led to cell aging and series of aging-related changes including proliferation inhibition, cell cycle G1 arrest and DNA damage. Mechanism research revealed DANCR binds with hNRNPC and p53, while DANCR knockdown attenuates the binding of hNRNPC and p53, thus enhancing protein level of p53 and promoting granulosa cells aging significantly. CONCLUSION: The newly identified lncRNA DANCR inhibits p53-dependent granulosa cells aging by regulating hNRNPC-p53 interaction, and eventually counteracting POI. This provides new insights into the pathogenesis of POI and provides a potential target for future diagnosis and treatment.

3,4-Methylenedioxy-ß-Nitrostyrene Alleviates Dextran Sulfate Sodium-Induced Mouse Colitis by Inhibiting the NLRP3 Inflammasome.

Inflammatory bowel disease (IBD) has been reported to be associated with NLRP3 inflammasome activation. Therefore inhibiting inflammasome activation could be a new approach to treat IBD. Inflammasome inhibitors NLRP3-IN-2, JC124, and 3,4-methylenedioxy-ß-nitrostyrene (MNS) were previously reported to exert anti-inflammatory effects in various disease models but not in the dextran sulfate sodium (DSS)-induced colitis model. Here, we showed that MNS was more efficient in inhibiting the secretion of interleukin-1ß (IL-1ß) by blocking oligomerization of apoptosis-associated speck-like protein (ASC) than NLRP3-IN-2 and JC124. To investigate the protective effects of MNS on enteritis, we administered intragastric MNS to DSS-induced colitis mice. The results demonstrated that MNS attenuated DSS-induced body weight loss, colon length shortening, and pathological damage. In addition, MNS inhibited the infiltration of macrophages and inflammatory cells and reduced IL-1ß and IL-12p40 pro-inflammatory cytokines but had no significant effect on tumor necrosis factor α (TNF-α) and IL-6. Furthermore, we also found that the differentiation of IL-17A+interferon-γ (IFN-γ)+CD4+ T cell was decreased in the colon after MNS treatment, which might be mediated by IL-1ß, etc. cytokine release. Taken together, MNS alleviated DSS-induced intestinal inflammation by inhibiting NLRP3 inflammasome activation, which may function as an effective therapeutic for IBD.

Novel LAT Pathogenic Variants in a POI Family and Its Role in the Ovary.

Premature ovarian insufficiency (POI) affects about 1% of women under 40 years and leads most often to definitive infertility with adverse health outcomes. Genetic factor has been reported to play an important role in POI. However, the genetic etiology remains unknown in the majority of the POI patients. Whole-exome sequencing and variant analysis were carried out in a POI pedigree. In vitro studies of the wild-type and mutant proteins were conducted in primary granulosa cells (GCs) and granulosa cell line. The result showed that the patients carried compound heterozygous nonsynonymous mutations (c.245C > T and c.181C > G) in LAT gene, which were identified to be transmitted from their parents. The two variants were assessed to affect residues that were conserved across different species examined, and were predicted to be deleterious by software predictions. Protein structure predicting result indicated that the two variants could alter their interactions with surrounding residues, which may change the internal structure of the LAT protein. Moreover, LAT protein expression in GCs was demonstrated for the first time, and further functional assays suggested that this mutation could reduce LAT expression and influence GC survival, which may contribute to the etiology of POI. In summary, we detect novel LAT pathogenic variants in a POI pedigree and report for the first time that LAT is present and functional in the GCs of the ovary. Our findings not only shed new light on the role of LAT in GCs, but also broaden the spectrum of genetic causes of POI.

Isoliquiritigenin alleviates P. gingivalis-LPS/ATP-induced pyroptosis by inhibiting NF-κB/ NLRP3/GSDMD signals in human gingival fibroblasts.

OBJECTIVE: To investigate whether pyroptosis is induced by Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS)/ adenosine triphosphate (ATP) through NF-κB/NLRP3/GSDMD signaling in human gingival fibroblasts (HGFs) and whether isoliquiritigenin (ISL) alleviates pyroptosis by inhibition of NF-κB/NLRP3/GSDMD signals. DESIGN: Periodontitis was optimally simulated using a combination of P. gingivalis-LPS and ATP. The expression levels of genes and proteins of NF-κB, NLRP3 inflammasome, GSDMD, and IL-1ß was characterized by qRT-PCR, western blotting and ELISA. The 2',7'­dichlorodihydrofluorescein diacetate fluorescence probe was used to determine the intracellular ROS level. Hoechst 33342 and PI double staining, cytotoxicity assay, and caspase-1 activity assay were used to confirm the influence of ISL on pyroptosis in P. gingivalis-LPS/ATP-treated HGFs. RESULTS: P. gingivalis-LPS/ATP stimulation significantly promoted expression of NF-κB, the NLRP3 inflammasome, GSDMD, and IL-1ß at gene and protein levels. The proportion of membrane-damaged cells, caspase-1 activity, and the release of lactate dehydrogenase (LDH) were also elevated. However, pretreatment with ISL observably suppressed these effects. CONCLUSIONS: P. gingivalis-LPS/ATP induced pyroptosis in HGFs by activating NF-κB/NLRP3/GSDMD signals and ISL attenuated P. gingivalis-LPS/ATP-induced pyroptosis by inhibiting these signals. This evidence may provide a new direction for the treatment of periodontitis.

Calcium-sensing receptor (CaSR) agonist R568 inhibits small intestinal motility of mice through neural and non-neural mechanisms.

Gastrointestinal motility (GI) disorder causes symptoms such as dyspepsia, abdominal distention, and constipation and severely affects quality of life. The calcium (Ca2+)-sensing receptor (CaSR) expressed in the digestive tract can be activated by amino acids and participates in GI motility regulation. This study is designed to explore the effect and underlying mechanism of CaSR agonist R568 on the small intestine motility of mice in vivo and ex vivo. R568 was given to male C57BL/6 mice by gavage or incubated with isolated jejunum and ileum segments to observe its effects on GI motility and the involved neurons, neurotransmitters and hormones were detected by fluorescence immunohistochemistry and enzyme-linked immunosorbent assays. The in vivo results showed that the intestinal propulsive rate reduced in response to oral intake of R568. R568 treatment increased the numbers of nitric oxide synthase-positive neurons and nitric oxide release but decreased the choline acetyl transferase-positive neurons and acetylcholine release in the myenteric plexuses. R568 increased the secretion of cholecystokinin in the intestinal tissues and serum but had no effect on the secretion of glucagon like peptide-1. Ex vivo results showed that R568 inhibited the contractility of intestinal strips from the jejunum and ileum. Nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester (L-NAME), M-receptor antagonist-atropine, and tetrodotoxin (TTX) failed to block the effect of R568. CaSR co-expressed with interstitial cells of Cajal (ICCs) in the myenteric plexus suggests the possibility that ICCs mediated the effect of R568. Our findings demonstrate that CaSR activation inhibited intestinal motility, and both the enteric nervous system and non-neural mechanism are involved in this process.

The m6A mRNA demethylase FTO in granulosa cells retards FOS-dependent ovarian aging.

Multifunctional N6-methyladenosine (m6A) has been revealed to be an important epigenetic component in various physiological and pathological processes, but its role in female ovarian aging remains unclear. Thus, we demonstrated m6A demethylase FTO downregulation and the ensuing increased m6A in granulosa cells (GCs) of human aged ovaries, while FTO-knockdown GCs showed faster aging-related phenotypes mediated. Using the m6A-RNA-sequence technique (m6A-seq), increased m6A was found in the FOS-mRNA-3'UTR, which is suggested to be an erasing target of FTO that slows the degradation of FOS-mRNA to upregulate FOS expression in GCs, eventually resulting in GC-mediated ovarian aging. FTO acts as a senescence-retarding protein via m6A, and FOS knockdown significantly alleviates the aging of FTO-knockdown GCs. Altogether, the abovementioned results indicate that FTO in GCs retards FOS-dependent ovarian aging, which is a potential diagnostic and therapeutic target against ovarian aging and age-related reproductive diseases.

Exogenous Orexin-A Microinjected Into Central Nucleus of the Amygdala Modulates Feeding and Gastric Motility in Rats.

Orexin-A is a circulating neuropeptide and neurotransmitter that regulates food intake and gastric motility. The central nucleus of the amygdala (CeA), which regulates feeding behavior and gastric function, expresses the orexin-1 receptor. The aim of this study was to evaluate the effects of microinjection of exogenous orexin-A into the CeA, on food intake and gastric motility, and to explore the mechanisms of these effects. Normal chow and high fat food (HFF) intake were measured, gastric motility and gastric emptying were evaluated, extracellular single unit firing was recorded, and c-fos expression was determined. The results showed that microinjection of orexin-A into the CeA resulted in increased HFF intake but did not affect normal chow intake. This effect was blocked by an orexin-1 receptor antagonist-SB-334867 and was partially blocked by a dopamine D1 receptor antagonist-SCH-23390. Gastric motility and gastric emptying were enhanced by orexin-A, and the former effect was abolished by subdiaphragmatic vagotomy. The firing frequency of gastric distention-related neurons was regulated by orexin-A via the orexin-1 receptor. Furthermore, c-fos expression was increased in the ventral tegmental area (VTA) and the nucleus accumbens (NAc), the lateral hypothalamus (LHA), and the dorsal motor nucleus of the vagus (DMV) in response to microinjection of orexin-A into the CeA. These findings showed that orexin-A regulated palatable food intake and gastric motility via the CeA. The LHA, the VTA, and the NAc may participate in palatable food intake and the CeA-DMV-vagus-stomach pathway may be involved in regulating gastric motility through the regulation of neuronal activity in the CeA.

The effect of doxycycline-containing chitosan/carboxymethyl chitosan nanoparticles on NLRP3 inflammasome in periodontal disease.

A polyelectrolyte complex nanoparticle comprising chitosan (CS) and carboxymethyl chitosan (CMCS) was prepared (CS/CMCS-NPs) by ionic gelation, which was then used as a doxycycline carrier (Dox:CS/CMCS-NPs). The obtained CS/CMCS-NPs and Dox:CS/CMCS-NPs were characterized for various parameters and bacteriostatic ability against Porphyromonas gingivalis. The regulation of related genes and proteins of NLRP3 inflammasome and IL-1ß in human gingival fibroblasts (HGFs) was characterized by qRT-PCR, western blotting and ELISA. The results showed that Dox:CS/CMCS-NPs had an orderly morphology and an excellent cytocompatibility. P. gingivalis was strongly inhibited by Dox:CS/CMCS-NPs contrasted with control group. Dox:CS/CMCS-NPs effectively down-regulated both gene and protein levels of NLRP3 inflammasome and IL-1ß in HGFs. This study provides a new method for rational application of Dox in the clinical treatment of periodontal disease and a new direction for explaining the mechanism of action of Dox:CS/CMCS-NPs and more drug-carrying nanoparticles.

CD24: a marker of granulosa cell subpopulation and a mediator of ovulation.

Granulosa cells (GCs) play a critical role in driving the formation of ovarian follicles and building the cumulus-oocyte complex surrounding the ovum. We are particularly interested in assessing oocyte quality by examining the detailed gene expression profiles of human cumulus single cells. Using single-cell RNAseq techniques, we extensively investigated the single-cell transcriptomes of the cumulus GC populations from two women with normal ovarian function. This allowed us to elucidate the endogenous heterogeneity of GCs by uncovering the hidden GC subpopulation. The subsequent validation results suggest that CD24(+) GCs are essential for triggering ovulation. Treatment with human chorionic gonadotropin (hCG) significantly increases the expression of CD24 in GCs. CD24 in cultured human GCs is associated with hCG-induced upregulation of prostaglandin synthase (ARK1C1, PTGS2, PTGES, and PLA2G4A) and prostaglandin transporter (SLCO2A1 and ABCC4) expression, through supporting the EGFR-ERK1/2 pathway. In addition, it was observed that the fraction of CD24(+) cumulus GCs decreases in PCOS patients compared to that of controls. Altogether, the results support the finding that CD24 is an important mediator of ovulation and that it may also be used for therapeutic target of ovulatory disorders.

The role of autophagy in pro-inflammatory responses of microglia activation via mitochondrial reactive oxygen species in vitro.

Microglia over-activation contributes to neurodegenerative processes by neurotoxin factors and pro-inflammatory molecules of pro-inflammatory processes. Mitochondrial reactive oxygen species (ROS) and autophagy pathway might be involved in microglial activation, but the underlying mechanism is unclear. Here, we regulated autophagy pathway of microglia in vitro by autophagy inhibition (3-methyladenine treatment, siRNA-Beclin 1 or siRNA-ATG5 transfection) or induction (rapamycin treatment) in murine microglial BV-2 cells or cultured primary mouse microglial cells. And we found that autophagy inhibition could sensitize mitochondrial profile and microglial activation of cultured microglial cells, demonstrated by significant production of mitochondrial ROS, loss of mitochondrial membrane potential, secretion of pro-inflammatory cytokines including interleukin 1ß (IL-1ß), interleukin 6 (IL-6), interleukin 12 (IL-12) and tumor necrosis factor α and marked activation of mitogen-activated proteinkinases (MAPKs) and nuclear factor κB (NF-κB). These effects could be blocked by specific inhibitors of MAPK and NF-κB or mitochondrial antioxidants, Mito-TEMPO. Meanwhile, induction of autophagy with rapamycin treatment could significantly suppress microglial inflammatory responses, mitochondrial ROS production, activation of MAPKs and NF-κB. Taken together, our in vitro results from primary cultured microglia and BV-2 cell lines indicated that autophagy inhibition might participate in brain macrophage or microglia over-activation and mitochondrial ROS generation might be involved in the regulatory microglial pro-inflammatory responses.

Endothelia-Targeting Protection by Escin in Decompression Sickness Rats.

Endothelial dysfunction is involved in the pathogenesis of decompression sickness (DCS) and contributes substantively to subsequent inflammatory responses. Escin, the main active compound in horse chestnut seed extract, is well known for its endothelial protection and anti-inflammatory properties. This study aimed to investigate the potential protection of escin against DCS in rats. Escin was administered orally to adult male rats for 7 d (1.8 mg/kg/day) before a simulated air dive. After decompression, signs of DCS were monitored, and blood and pulmonary tissue were sampled for the detection of endothelia related indices. The incidence and mortality of DCS were postponed and decreased significantly in rats treated with escin compared with those treated with saline (P < 0.05). Escin significantly ameliorated endothelial dysfunction (increased serum E-selectin and ICAM-1 and lung Wet/Dry ratio, decreased serum NO), and oxidative and inflammatory responses (increased serum MDA, MPO, IL-6 and TNF-α) (P < 0.05 or P < 0.01). The results suggest escin has beneficial effects on DCS related to its endothelia-protective properties and might be a drug candidate for DCS prevention and treatment.

Endothelial dysfunction correlates with decompression bubbles in rats.

Previous studies have documented that decompression led to endothelial dysfunction with controversial results. This study aimed to clarify the relationship between endothelial dysfunction, bubble formation and decompression rate. Rats were subjected to simulated air dives with one of four decompression rates: one slow and three rapid. Bubble formation was detected ultrasonically following decompression for two hours, before measurement of endothelial related indices. Bubbles were found in only rapid-decompressed rats and the amount correlated with decompression rate with significant variability. Serum levels of ET-1, 6-keto-PGF1α, ICAM-1, VCAM-1 and MDA, lung Wet/Dry weight ratio and histological score increased, serum NO decreased following rapid decompression. Endothelial-dependent vasodilatation to Ach was reduced in pulmonary artery rings among rapid-decompressed rats. Near all the above changes correlated significantly with bubble amounts. The results suggest that bubbles may be the causative agent of decompression-induced endothelial damage and bubble amount is of clinical significance in assessing decompression stress. Furthermore, serum levels of ET-1 and MDA may serve as sensitive biomarkers with the capacity to indicate endothelial dysfunction and decompression stress following dives.

Electron transport chain inhibitors induce microglia activation through enhancing mitochondrial reactive oxygen species production.

Reactive oxygen species (ROS) are believed to be mediators of excessive microglial activation, yet the resources and mechanism are not fully understood. Here we stimulated murine microglial BV-2 cells and primary microglial cells with different inhibitors of electron transport chain (ETC), rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, and NaN3 to induce mitochondrial ROS production and we observed the role of mitochondrial ROS in microglial activation. Our results showed that ETC inhibitors resulted in significant changes in cell viability, microglial morphology, cell cycle arrest and mitochondrial ROS production in a dose-dependent manner in both primary cultural microglia and BV-2 cell lines. Moreover, ETC inhibitors, especially rotenone and antimycin A stimulated secretion of interleukin 1ß (IL-1ß), interleukin 6 (IL-6), interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) by microglia with marked activation of mitogen-activated proteinkinases (MAPKs) and nuclear factor κB (NF-κB), which could be blocked by specific inhibitors of MAPK and NF-κB and mitochondrial antioxidants, Mito-TEMPO. Taken together, our results demonstrated that inhibition of mitochondrial respiratory chain in microglia led to production of mitochondrial ROS and therefore may activate MAPK/NF-кB dependent inflammatory cytokines release in microglia, which indicated that mitochondrial-derived ROS were contributed to microglial activation.

Does amifostine have radioprotective effects on salivary glands in high-dose radioactive iodine-treated differentiated thyroid cancer.

OBJECTIVES: To assess the effects of amifostine on salivary glands in radioactive iodine-treated differentiated thyroid cancer. METHODS: We searched the MEDLINE, EMBASE and the Cochrane Library for randomized controlled clinical trials which compared the effects of amifostine with those of placebo or acid-stimulating agents. RESULTS: Two randomized controlled clinical trials with a total of 130 patients were included. Both studies had a low risk of bias. There were no statistically significant differences between the effects of amifostine and acid-stimulating agents on the incidence of xerostomia (RR 0.24, 95% CI 0.01 to 9.52), the decrease of scintigraphically measured uptake of (99m)Tc by the parotid (RR 0.30, 95% CI -2.28 to 2.88) or submandibular glands (RR 1.90, 95% CI -1.46 to 5.26) at 12 months, or the reduction in blood pressure (RR 5.00, 95% CI 0.25 to 99.16). Neither of the included trials investigated death from any cause, morbidity, health-related quality of life or costs. CONCLUSION: The results of two randomized controlled clinical trials suggest that amifostine has no significant radioprotective effects on salivary glands in radioactive iodine treatment of differentiated thyroid cancer. The use of acid-stimulating agents to increase salivation should remain the first choice during radioactive iodine treatment of differentiated thyroid cancer. Patients should also be well informed of the importance of hydration and acid stimulation.

Relationships between MMP-2, MMP-9, TIMP-1 and TIMP-2 levels and their pathogenesis in patients with lupus nephritis.

Recent evidence suggests that matrix metalloproteinases (MMPs) were involved with many kinds of kidney diseases. We investigated the roles of MMPs and its tissue inhibitors TIMPs in patients with lupus nephritis (LN). A total of 44 systemic lupus erythematosus patients and 31 healthy subjects were enrolled. The levels of total MMP-2, 9 (tMMP-2, tMMP-9) along with TIMP-1, 2 were measured in serum by ELISA. Serum tMMP-2, tMMP-9 was higher in LN patients than those non-LN patients and healthy controls. Serum tMMP-2 in patients without LN was higher than in healthy controls. TIMP-2 was higher in LN patients than healthy controls, and no significant difference in TIMP-2 was observed between LN and non-LN patients. TIMP-1 levels among LN, non-LN patients and healthy controls were comparable. The ratio of tMMP-9 to TIMP-1 in LN patients was higher than non-LN patients and healthy controls and no difference in ratio of tMMP-9 to TIMP-1 between non-LN patients and healthy subjects was observed. A negative correlation between the ratio of tMMP-9 to TIMP-1 in lupus patients and the titers of anti-dsDNA was found; whereas, no correlation between the ratio of tMMP-9 to TIMP-1 and the concentration of C3 as well 24 h urine protein was observed in LN patients. We suggest imbalance between tMMP-9 and TIMP-1 may contribute to the pathogenesis of LN. Measurement of MMPs and TIMPs may be helpful in the early identification of lupus patients with LN and may help gauge the response to treatment in patients with active LN undergoing treatment.