ABSTRACT
Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with the AGE-Apt or control-aptamer for 6 weeks and were then sacrificed. Plasma glucose, testicular AGEs, and Rage gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice, the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing AGE-RAGE-induced oxidative stress and inflammation in the testes of DM mice.
Subject(s)
Aptamers, Nucleotide , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Glycation End Products, Advanced , Inflammation , Oxidative Stress , Receptor for Advanced Glycation End Products , Sperm Motility , Testis , Animals , Male , Oxidative Stress/drug effects , Glycation End Products, Advanced/metabolism , Mice , Aptamers, Nucleotide/pharmacology , Testis/metabolism , Testis/drug effects , Testis/pathology , Receptor for Advanced Glycation End Products/metabolism , Diabetes Mellitus, Experimental/metabolism , Sperm Motility/drug effects , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Inflammation/metabolism , Inflammation/pathology , Spermatozoa/metabolism , Spermatozoa/drug effects , Sperm CountABSTRACT
Introduction: Hand, foot, and mouth disease generally occurs in children. In rare cases, hand, foot, and mouth disease affects the testicles. Case presentation: A 29-year-old man presented to our emergency department with testicular pain for several days after the onset of hand, foot, and mouth disease. Ultrasonography revealed hypoechoic mass-like areas in the right testis. A mild inflammatory response was noted, tumor markers and urinary data were normal, and tests for infection were all negative. Antibiotics were initiated and ultrasonography was performed in every subsequent examination. Testicular pain disappeared 6 months later. Conclusion: We encountered a rare case of a testicular lesion related to hand, foot, and mouth disease that was successfully treated. The careful selection of treatment for testicular pain and scrotal enlargement in young adult males, such as surgery and symptomatic treatment, based on their medical history and laboratory findings, is important.
ABSTRACT
Tokophobia is regarded as the intensive fear of childbirth that some pregnant women have. However, little is known about the psychopathological details of tokophobia (fear of childbirth). Between 2020 and 2021, a total of 10 pregnant women (nine nulliparae and one multipara) with a strong fear of childbirth were referred by obstetricians. Semi-structured psychopathological interviews were conducted, and two cases were judged to have obsession, three an overvalued idea, and one secondary delusion. Three were characterised by both obsession and overvalued idea and one by both obsession and secondary delusion. In total, six cases had features of an overvalued idea. All of the participants except one had a lifetime history of a specific phobia. In addition, their history included social phobia in two cases, panic disorder in one case, obsessive-compulsive disorder (other than tokophobia) in two cases, depressive disorder in two cases, bipolar disorder in two cases, and PTSD in six cases. To conclude, this study showed that tokophobia was not a phobic disorder but a kind of overvalued idea that requires specific assessment and treatment.
ABSTRACT
We have developed DNA aptamers that can inhibit the toxic effects of advanced glycation end products (AGE-Apts). We herein evaluated the effects of AGE-Apts on muscle mass and strength in senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old male SAMP8 mice received subcutaneous infusion of control DNA aptamers (CTR-Apts) or AGE-Apts. Mice in an age-matched senescence-accelerated mouse resistant strain 1 (SAMR1) group were treated with CTR-Apts as controls. The soleus muscles were collected after the 8-week intervention for weight measurement and histological, RT-PCR, and immunofluorescence analyses. Grip strength was measured before and after the 8-week intervention. AGE-Apt treatment inhibited the progressive decrease in the grip strength of SAMP8 mice. SAMP8 mice had lower soleus muscle weight and fiber size than SAMR1 mice, which was partly restored by AGE-Apt treatment. Furthermore, AGE-Apt-treated SAMP8 mice had a lower interstitial fibrosis area of the soleus muscle than CTR-Apt-treated SAMP8 mice. The soleus muscle levels of AGEs, oxidative stress, receptor for AGEs, and muscle ring-finger protein-1 were increased in the CTR-Apt-treated mice, all of which, except for AGEs, were inhibited by AGE-Apt treatment. Our present findings suggest that the subcutaneous delivery of AGE-Apts may be a novel therapeutic strategy for aging-related decrease in skeletal muscle mass and strength.
ABSTRACT
The Edinburgh Postnatal Depression Scale (EPDS) is a widely used screening tool for perinatal depression. Its factor structure is still a debatable topic. Our study aimed to examine the factor structure and measurement invariances of the Japanese version of the EPDS from late pregnancy to early postpartum. A total of 633 women were followed with the EPDS at three times over the perinatal period: late pregnancy (n = 633), 5 days after childbirth (n = 445), and 1 month after childbirth (n = 392). We randomly divided the participants into two groups: one for exploratory factor analyses (EFAs) and another for confirmatory factor analyses (CFAs). The result of the EFAs indicated different factor models at each time point. Hence, CFAs were performed using the second sample set to compare different models including the ones previously reported. A 3-factor model consisting of depression (items 7, 9), anxiety (items 4, 5), and anhedonia (items 1, 2) (Kubota et al., 2018) was consistently stable during the whole perinatal period. Kubota's 3-factor model showed invariance across the perinatal period.
ABSTRACT
SMTP-44D has been reported to have anti-oxidative and anti-inflammatory reactions, including reduced expression of receptor for advanced glycation end products (RAGE) in experimental diabetic neuropathy. Although activation of RAGE with its ligands, and advanced glycation end products (AGEs), play a crucial role in atherosclerotic cardiovascular disease, a leading cause of death in diabetic patients, it remains unclear whether SMTP-44D could inhibit experimental atherosclerosis by suppressing the AGEs-RAGE axis. In this study, we investigated the effects of SMTP-44D on atherosclerotic plaque formation and expression of AGEs in apolipoprotein-E null (Apoe-/-) mice. We further studied here whether and how SMTP-44D inhibited foam cell formation of macrophages isolated from Apoe-/- mice ex vivo. Although administration of SMTP-44D to Apoe-/- mice did not affect clinical or biochemical parameters, it significantly decreased the surface area of atherosclerotic lesions and reduced the atheromatous plaque size, macrophage infiltration, and AGEs accumulation in the aortic roots. SMTP-44D bound to immobilized RAGE and subsequently attenuated the interaction of AGEs with RAGE in vitro. Furthermore, foam cell formation evaluated by Dil-oxidized low-density lipoprotein (ox-LDL) uptake, and gene expression of RAGE, cyclin-dependent kinase 5 (Cdk5) and CD36 in macrophages isolated from SMTP-44D-treated Apoe-/- mice were significantly decreased compared with those from saline-treated mice. Gene expression levels of RAGE and Cdk5 were highly correlated with each other, the latter of which was also positively associated with that of CD36. The present study suggests that SMTP-44D may inhibit atherosclerotic plaque formation in Apoe-/- mice partly by blocking the AGEs-RAGE-induced ox-LDL uptake into macrophages via the suppression of Cdk5-CD36 pathway.
Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Animals , Mice , Plaque, Atherosclerotic/genetics , Plaque, Atherosclerotic/complications , Receptor for Advanced Glycation End Products/genetics , Receptor for Advanced Glycation End Products/metabolism , Atherosclerosis/metabolism , Lipoproteins, LDL , Glycation End Products, Advanced/metabolism , Apolipoproteins E/metabolism , Apolipoproteins , Mice, KnockoutABSTRACT
Intense fear of childbirth by expectant women is called tokophobia. Because there are no qualitative studies targeting women with an intense fear of childbirth in Japan, it is unknown whether there is any link between the type of fear of objects/situations among tokophobic women and their psychological/demographic background. Furthermore, there is no available summary of the lived experience of Japanese women with tokophobia. This study aims to identify the intensity patterns of various types of fear among the participants and summarize the lived experience of having intense fear of childbirth. A qualitative descriptive study was conducted using a semi-structured interview. Pregnant women with an intense fear of childbirth participated in individual interviews facilitated by a psychiatrist and a midwife. Audio recordings of the interviews were transcribed and analyzed using a content analysis approach. The number of participants was ten. The types of feared objects varied individually and these were categorized as being related to either prospective or retrospective fear. The participants' experiences were grouped into three categories: difficulty in daily life, preoccupied negative expectation towards childbirth, and psychological adaptation to the upcoming childbirth. The results imply that women with tokophobia continuously suffer from fear in their daily life; hence, a special approach is needed to detect and reduce their fear.
ABSTRACT
A new species of the stenopodid shrimp genus Odontozona Holthuis, 1946 is described and illustrated on the basis of single specimen recently collected from a submarine cave at Shimoji-jima Island, Miyako Island Group, Ryukyu Islands, southwestern Japan. Odontozona ganzu sp. nov. appears to be unique within the genus Odontozona by lacking transverse row of posterior small spines on sixth pleuron. General morphology of the new species is also similar to O. stigmatica Saito, Okuno Anker, 2017 described from Ishigaki-jima Island, Ryukyu Islands, West Pacific, but differs from it by a combination of morphological characters, viz., lacking the cincture of small spines on the posterior margin of the carapace, the distinct transverse carina on the third pleuron, as well as the lateral teeth of the uropodal endopod. This study increases the total number of the described species in the genus Odontozona to 23, 11 of which occur the Indo-West Pacific.
Subject(s)
Decapoda , Ecosystem , Animal Distribution , Animal Structures/anatomy & histology , Animals , Organ SizeABSTRACT
OBJECTIVE: Sodium-glucose cotransporter-2 (SGLT2) inhibitors exhibit cardioprotective properties in patients with diabetes. However, SGLT2 is not expressed in the heart, and the underlying molecular mechanisms are not fully understood. We investigated whether the SGLT2 inhibitor luseogliflozin exerts beneficial effects on high glucose-exposed cardiomyocytes via the suppression of sodium-hydrogen exchanger-1 (NHE-1) activity. METHODS: Mouse cardiomyocytes were incubated under normal or high glucose conditions with vehicle, luseogliflozin, or the NHE-1 inhibitor cariporide. NHE-1 activity and gene expression were evaluated by the SNARF assay and real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis, respectively. Six-week-old male db/db mice were treated with vehicle or luseogliflozin for 6 weeks, and the hearts were collected for histological, RT-PCR, and western blot analyses. RESULTS: High glucose increased NHE-1 activity and transforming growth factor (Tgf)-ß2 mRNA levels in cardiomyocytes, both of which were inhibited by luseogliflozin or cariporide, whereas their combination showed no additive suppression of Tgf-ß2 mRNA levels. Luseogliflozin attenuated cardiac hypertrophy and fibrosis in db/db mice in association with decreased mRNA and protein levels of TGF-ß2. CONCLUSIONS: Luseogliflozin may suppress cardiac hypertrophy in diabetes by reducing Tgf-ß2 expression in cardiomyocytes via the suppression of NHE-1 activity.
Subject(s)
Diabetes Mellitus , Myocytes, Cardiac , Sodium-Hydrogen Exchanger 1/metabolism , Animals , Cardiomegaly/pathology , Diabetes Mellitus/metabolism , Glucose/metabolism , Glucose/pharmacology , Humans , Male , Mice , Myocytes, Cardiac/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sodium-Glucose Transporter 2/metabolism , Sodium-Glucose Transporter 2/pharmacology , Sorbitol/analogs & derivatives , Transforming Growth Factor beta2/metabolism , Transforming Growth Factor beta2/pharmacologyABSTRACT
Tumor necrosis frequently occurs in malignant tumors, showing rapid growth and invasion. This phenomenon is generally regarded as simple ischemic necrosis due to insufficient tumor vessels and blood supply. However, the necrotic tissue contains high amount of nuclear substances, DNA, and nucleoproteins that may affect the surrounding tumor cells by promoting or suppressing the tumor cell growth in vivo. This study focused on the effects of an externally administered water-soluble nuclear crude extract (SNE) containing nuclear protein and oligonucleotides on several human cancer and noncancer cell lines. The results demonstrated that the SNE suppressed cell growth in cancer and noncancer cells in vitro. Through the flow cytometry analysis of the nuclear DNA content, it was observed that the SNE increased and decreased cell proportion in the S and G2/M phases, respectively, thereby suggesting that the cell growth inhibition was due to cell cycle delay, and not due to apoptosis. These studies suggest that the high-concentration of extracellular nucleotides generated as a result of tumor necrosis and/or released from infiltrated neutrophils could suppress the growth of surrounding cancer and intrinsic cells, which provides us some insights into an alternative anticancer strategy for patients with highly malignant necrotic tumor.
ABSTRACT
Glucose-dependent insulinotropic polypeptide (GIP) has been reported to have an atheroprotective property in animal models. However, the effect of GIP on macrophage foam cell formation, a crucial step of atherosclerosis, remains largely unknown. We investigated the effects of GIP on foam cell formation of, and CD36 expression in, macrophages extracted from GIP receptor-deficient (Gipr-/-) and Gipr+/+ mice and cultured human U937 macrophages by using an agonist for GIP receptor, [D-Ala2]GIP(1-42). Foam cell formation evaluated by esterification of free cholesterol to cholesteryl ester and CD36 gene expression in macrophages isolated from Gipr+/+ mice infused subcutaneously with [D-Ala2]GIP(1-42) were significantly suppressed compared with vehicle-treated mice, while these beneficial effects were not observed in macrophages isolated from Gipr-/- mice infused with [D-Ala2]GIP(1-42). When macrophages were isolated from Gipr+/+ and Gipr-/- mice, and then exposed to [D-Ala2]GIP(1-42), similar results were obtained. [D-Ala2]GIP(1-42) attenuated ox-LDL uptake of, and CD36 gene expression in, human U937 macrophages as well. Gene expression level of cyclin-dependent kinase 5 (Cdk5) was also suppressed by [D-Ala2]GIP(1-42) in U937 cells, which was corelated with that of CD36. A selective inhibitor of Cdk5, (R)-DRF053 mimicked the effects of [D-Ala2]GIP(1-42) in U937 cells. The present study suggests that GIP could inhibit foam cell formation of macrophages by suppressing the Cdk5-CD36 pathway via GIP receptor.
ABSTRACT
Diabetic cardiomyopathy is associated with an increased risk for heart failure and death in patients with diabetes. We investigated here whether and how GIP attenuated cardiac hypertrophy and fibrosis in diabetic mice with obesity. Diabetic db/db mice at 7 weeks old were infused with vehicle or GIP (50 nmol/kg/day) for 6 weeks, and hearts were collected for histological and RT-PCR analyzes. Cardiomyocytes isolated from neonatal mice were incubated with or without 300 nM [D-Ala2]-GIP, 30 mM glucose, or 100 µg/mL advanced glycation end products (AGEs) for RT-PCR and lucigenin assays. Compared with non-diabetic mice, diabetic mice exhibited larger left ventricle wall thickness and cardiomyocyte sizes and more fibrotic areas in association with up-regulation of myosin heavy chain ß (ß-Mhc) and transforming growth factor-beta2 (Tgf-ß2) mRNA levels, all of which were inhibited by GIP infusion. High glucose increased NADPH oxidase-driven superoxide generation and up-regulated ß-Mhc, Tgf-ß2, and receptor for AGEs mRNA levels in cardiomyocytes, and augmented the AGE-induced ß-Mhc gene expression. [D-Ala2]-GIP attenuated all of the deleterious effects of high glucose and/or AGEs on cardiomyocytes. Our present findings suggest that GIP could inhibit cardiac hypertrophy and fibrosis in diabetic mice via suppression of TGF-ß2.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Animals , Cardiomegaly/prevention & control , Diabetic Cardiomyopathies/genetics , Diabetic Cardiomyopathies/prevention & control , Fibrosis , Glucose , Humans , Mice , Myocytes, Cardiac , Transforming Growth Factor beta2/geneticsABSTRACT
AIMS: This systematic review aimed to evaluate randomized controlled trials (RCTs) to examine the effect of maternal and infant sleep intervention during women's pregnancy for the purpose of preventing perinatal depression. METHOD: A systematic search (from inception to January 28, 2019) for RCTs using five electronic databases-the Cochrane Controlled Register of Trials (CENTRAL), Embase, PubMed, PsycINFO, and Ichushi Web (Japan Medical Abstracts Society)-was conducted. Twelve investigators independently conducted initial screenings based on title and abstract, and then, two researchers performed full-text reviews one by one. A meta-analysis would be conducted if at least three studies were found. However, only two articles that met inclusion criteria, and narrative data synthesis was conducted for these two articles. The study protocol has been registered at PROSPERO (CRD42019119999). RESULT: A total of 13 654 studies were initially searched. After removing duplicates, 10 547 studies were screened, and finally, two studies met the inclusion criteria. In both studies, the intervention was a one-time face-to-face session during pregnancy to deliver the behavioral knowledge and skills for optimizing sleep hygiene for both infant and mother. Effectiveness of the intervention in improving maternal mood was not significant in one study. In the other, there was a significant difference in maternal mood between the intervention and control group. No mood comparison was made between baseline and postintervention. CONCLUSION: This study found limited evidence to support the effectiveness of sleep intervention for all pregnant women, which means "universal intervention," to protect maternal mental health. Further well-designed RCTs are needed to confirm these findings.
Subject(s)
Depressive Disorder/prevention & control , Patient Education as Topic/statistics & numerical data , Pregnancy Complications/prevention & control , Psychotherapy, Brief/statistics & numerical data , Sleep Wake Disorders/prevention & control , Female , Humans , PregnancyABSTRACT
Advanced glycation end products (AGEs) are localized in macrophage-derived foam cells within atherosclerotic lesions, which could be associated with the increased risk of atherosclerotic cardiovascular disease under diabetic conditions. Although foam cell formation of macrophages has been shown to be enhanced by AGEs, the underlying molecular mechanism remains unclear. Since cyclin-dependent kinase 5 (Cdk5) is reported to modulate inflammatory responses in macrophages, we investigated whether Cdk5 could be involved in AGE-induced CD36 gene expression and foam cell formation of macrophages. AGEs significantly increased Dil-oxidized low-density lipoprotein (ox-LDL) uptake, and Cdk5 and CD36 gene expression in U937 human macrophages, all of which were inhibited by DNA aptamer raised against RAGE (RAGE-aptamer). Cdk5 and CD36 gene expression levels were correlated with each other. An antioxidant, N-acetyl-l-cysteine, mimicked the effects of RAGE-aptamer on AGE-exposed U937 cells. A selective inhibitor of Cdk5, (R)-DRF053, attenuated the AGE-induced Dil-ox-LDL uptake and CD36 gene expression, whereas anti-CD36 antibody inhibited the Dil-ox-LDL uptake but not Cdk5 gene expression. The present study suggests that AGEs may stimulate ox-LDL uptake into macrophages through the Cdk5-CD36 pathway via RAGE-mediated oxidative stress.
Subject(s)
CD36 Antigens/metabolism , Cyclin-Dependent Kinase 5/metabolism , Glycation End Products, Advanced/metabolism , Lipoproteins, LDL/metabolism , Macrophages/metabolism , Oxidative Stress , Receptor for Advanced Glycation End Products/metabolism , Animals , Aptamers, Nucleotide , CD36 Antigens/genetics , Cyclin-Dependent Kinase 5/genetics , Humans , Models, Biological , U937 CellsABSTRACT
Although glucagon has been shown to exert pleiotropic actions in various types of cells and organs through the interaction with its receptor, its pathophysiological role in atherosclerotic cardiovascular disease remains unclear. Here, we examined whether and how glucagon could attenuate the progression of atherosclerotic plaques in apolipoprotein E-deficient mice (ApoE-/-), an animal model of atherosclerosis. Glucagon (138 or 413 nmol/kg/day) or vehicle was infused to mice at 16 weeks of age. After 4-week treatment, vascular samples were collected for histological and RT-PCR analyses. Human monocytic THP-1 cells were pre-incubated with or without a glucagon receptor antagonist L-168049, and then treated with or without glucagon for 7 h. Gene and protein expressions were determined by RT-PCR and western blot analyses, respectively. High-dose glucagon infusion significantly decreased aortic plaque area and volume in ApoE-/- mice, both of which were inversely correlated with plasma glucagon levels. Glucagon infusion also reduced the ratio of pro-inflammatory interleukin-1ß to anti-inflammatory interleukin-10 gene expression in aortae. Glucagon receptor was expressed in THP-1 cells, and 1 nM glucagon decreased the ratio of interleukin-1ß to interleukin-10 gene expression, which was significantly prevented by L-168049. Our present findings suggest that glucagon could exert atheroprotection partly via its anti-inflammatory property.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Aorta/drug effects , Aortic Diseases/prevention & control , Atherosclerosis/prevention & control , Glucagon/administration & dosage , Receptors, Glucagon/agonists , Animals , Aorta/metabolism , Aorta/pathology , Aortic Diseases/metabolism , Aortic Diseases/pathology , Atherosclerosis/metabolism , Atherosclerosis/pathology , Disease Models, Animal , Humans , Inflammation Mediators/metabolism , Interleukin-10/genetics , Interleukin-10/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Male , Mice, Inbred BALB C , Mice, Knockout, ApoE , Receptors, Glucagon/metabolism , THP-1 CellsABSTRACT
Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to play a protective role against atherosclerosis in both animal models and patients with type 2 diabetes (T2D). However, since T2D is associated with dyslipidemia, hypertension and insulin resistance, part of which are ameliorated by DPP-4 inhibitors, it remains unclear whether DPP-4 inhibitors could have anti-atherosclerotic properties directly by attenuating the harmful effects of hyperglycemia. Therefore, we examined whether a DPP-4 inhibitor, teneligliptin, could suppress oxidized low-density lipoprotein (ox-LDL) uptake, foam cell formation, CD36 and acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) gene expression of macrophages isolated from streptozotocin-induced type 1 diabetes (T1D) mice and T1D patients as well as advanced glycation end product (AGE)-exposed mouse peritoneal macrophages and THP-1 cells. Foam cell formation, CD36 and ACAT-1 gene expression of macrophages derived from T1D mice or patients increased compared with those from non-diabetic controls, all of which were inhibited by 10 nmol/L teneligliptin. AGEs mimicked the effects of T1D; teneligliptin attenuated all the deleterious effects of AGEs in mouse macrophages and THP-1 cells. Our present findings suggest that teneligliptin may inhibit foam cell formation of macrophages in T1D via suppression of CD36 and ACAT-1 gene expression partly by attenuating the harmful effects of AGEs.
Subject(s)
CD36 Antigens/metabolism , Diabetes Mellitus, Type 1/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Foam Cells/drug effects , Macrophages, Peritoneal/drug effects , Sterol O-Acyltransferase/metabolism , Animals , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Foam Cells/metabolism , Glycation End Products, Advanced/metabolism , Humans , Macrophages, Peritoneal/metabolism , Male , Mice , Mice, Inbred C57BL , Pyrazoles/pharmacology , THP-1 Cells/drug effects , THP-1 Cells/metabolism , Thiazolidines/pharmacologyABSTRACT
BACKGROUND: The high prevalence and severe consequences of antenatal and postnatal depression makes their prevention critical. Previous systematic reviews and meta-analysis have shown the effects of psychological interventions on perinatal depression in individuals at risk. However, none have focused explicitly on universal prevention in the antenatal period. The purpose of this study is to conduct a systematic review and meta-analysis to clarify the effects of antenatal psychological interventions on perinatal depression, specifically focusing on universal prevention. METHODS: Four electronic databases, the Cochrane Controlled Register of Trials (CENTRAL), Embase, PubMed, and PsycINFO, were used to search for published randomized controlled trials from inception to January 28, 2019. Twelve investigators conducted the first screening from title and abstract, individually, and then NY and ZN performed full-text review one by one. For the meta-analysis, a random effect model was conducted by using Review Manager 5.3 for Windows. Subgroup analyses were also conducted for studies that employed a cognitive behavioral (CB) based approach. RESULTS: A total of 13,026 studies were initially searched. After removing duplicates, 9,919 studies were screened, and finally 18 studies met the inclusion criteria. The meta-analysis showed a significant effect of antenatal psychological intervention on both antenatal and postnatal depression (SMD = 0.28, 95% CI = 0.11 to 0.44, SMD = 0.37, 95% CI = 0.08 to 0.66) with moderate to high level of heterogeneity (I2 = 61%, p = 0.01; I2 = 84%, p < 0.001). For subgroup analysis, a significant effect of a CB based approach on antenatal depression was found in an antenatal period (SMD = 0.53, 95% CI = 0.13 to 0.94) with high heterogeneity (I2 = 85%, p = 0.001), while non-significant results were shown on postnatal depression (SMD = 0.45, 95% CI = -0.03 to 0.92). LIMITATIONS: Limitations include a language bias, as we included only studies published in English, and that the assessment of antenatal and postnatal depression using different methods caused high heterogeneity across studies. CONCLUSIONS: Psychological intervention in an antenatal period could be effective for universal prevention of both antenatal and postnatal depression. However, the results were still inconclusive due to relatively low methodological quality in the included studies. The evidence from more well-designed trials is needed in future studies.
Subject(s)
Cognitive Behavioral Therapy , Depression, Postpartum , Depressive Disorder , Depression , Depression, Postpartum/prevention & control , Depressive Disorder/prevention & control , Female , Humans , Mass Screening , Pregnancy , Psychosocial InterventionABSTRACT
BACKGROUND: Prevention of antenatal and postnatal depression is crucial, given its high prevalence and severe consequences. Although several systematic reviews and meta-analyses have examined the effects of psychological interventions on the population at risk for perinatal depression, few studies have focused on universal prevention and none have focused specifically on universal prevention in pregnancy. The aim of this study is to examine the effects of psychological interventions with a universal prevention focus on perinatal depression during pregnancy by performing a systematic review and meta-analysis based on both the latest articles and a broader literature search. METHODS: The literature search will be conducted using the Cochrane Controlled Register of Trials (CENTRAL), Embase, PubMed and PsycINFO, from inception onwards. Randomized controlled trials that examined the association between psychological interventions and universal prevention of antenatal and postnatal depression among pregnant women will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted following a priori defined methods in the protocol. DISCUSSION: The findings of this systematic review and meta-analysis will have both clinical and political importance in the context of perinatal mental health. In addition, this study will promote future studies and clarify the direction of research on universal prevention of perinatal depression. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019118041.
Subject(s)
Depression, Postpartum/prevention & control , Depressive Disorder/prevention & control , Meta-Analysis as Topic , Pregnancy Complications/prevention & control , Research Design , Systematic Reviews as Topic , Female , Humans , PregnancyABSTRACT
BACKGROUND: Excess fat deposition could induce phenotypic changes of perivascular adipose tissue (PVAT remodeling), which may promote the progression of atherosclerosis via modulation of adipocytokine secretion. However, it remains unclear whether and how suppression of PVAT remodeling could attenuate vascular injury. In this study, we examined the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor, luseogliflozin on PVAT remodeling and neointima formation after wire injury in mice. METHODS: Wilt-type mice fed with low-fat diet (LFD) or high-fat diet (HFD) received oral administration of luseogliflozin (18 mg/kg/day) or vehicle. Mice underwent bilateral femoral artery wire injury followed by unilateral removal of surrounding PVAT. After 25 days, injured femoral arteries and surrounding PVAT were analyzed. RESULTS: In LFD-fed lean mice, neither luseogliflozin treatment or PVAT removal attenuated the intima-to-media (I/M) ratio of injured arteries. However, in HFD-fed mice, luseogliflozin or PVAT removal reduced the I/M ratio, whereas their combination showed no additive reduction. In PVAT surrounding injured femoral arteries of HFD-fed mice, luseogliflozin treatment decreased the adipocyte sizes. Furthermore, luseogliflozin reduced accumulation of macrophages expressing platelet-derived growth factor-B (PDGF-B) and increased adiponectin gene expression. Gene expression levels of Pdgf-b in PVAT were correlated with the I/M ratio. CONCLUSIONS: Our present study suggests that luseogliflozin could attenuate neointimal hyperplasia after wire injury in HFD-fed mice partly via suppression of macrophage PDGF-B expression in PVAT. Inhibition of PVAT remodeling by luseogliflozin may be a novel therapeutic target for vascular remodeling after angioplasty.
Subject(s)
Adipose Tissue/drug effects , Adiposity/drug effects , Diet, High-Fat , Femoral Artery/drug effects , Neointima , Obesity/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sorbitol/analogs & derivatives , Vascular Remodeling/drug effects , Vascular System Injuries/drug therapy , Adiponectin/metabolism , Adipose Tissue/metabolism , Adipose Tissue/physiopathology , Animals , Disease Models, Animal , Femoral Artery/injuries , Femoral Artery/metabolism , Femoral Artery/physiopathology , Lymphokines/metabolism , Macrophages/drug effects , Macrophages/metabolism , Male , Mice, Inbred C57BL , Obesity/complications , Obesity/metabolism , Obesity/physiopathology , Platelet-Derived Growth Factor/metabolism , Sorbitol/pharmacology , Vascular System Injuries/complications , Vascular System Injuries/metabolism , Vascular System Injuries/physiopathologyABSTRACT
Nesfatin-1 is a novel anorexic peptide hormone that also exerts cardiovascular protective effects in rodent models. However, nesfatin-1 treatment at high doses also exerts vasopressor effects, which potentially limits its therapeutic application. Here, we evaluated the vasoprotective and vasopressor effects of nesfatin-1 at different doses in mouse models. Wild-type mice and those with the transgene nucleobindin-2, a precursor of nesfatin-1, were employed. Wild-type mice were randomly assigned to treatment with vehicle or nesfatin-1 at 0.2, 2.0 or 10 µg/kg/day (Nes-0.2, Nes-2, Nes-10, respectively). Subsequently, mice underwent femoral artery wire injury to induce arterial remodeling. After 4 weeks, injured arteries were collected for morphometric analysis. Compared with vehicle, nesfatin-1 treatments at 2.0 and 10 µg/kg/day decreased body weights and elevated plasma nesfatin-1 levels with no changes in systolic blood pressure. Furthermore, these treatments reduced neointimal hyperplasia without inducing undesirable remodeling in injured arteries. However, nesfatin-1 treatment at 0.2 µg/kg/day was insufficient to elevate plasma nesfatin-1 levels and showed no vascular effects. In nucleobindin-2-transgenic mice, blood pressure was slightly higher but neointimal area was lower than those observed in littermate controls. In cultured human vascular endothelial cells, nesfatin-1 concentration-dependently increased nitric oxide production. Additionally, nesfatin-1 increased AMP-activated protein kinase phosphorylation, which was abolished by inhibiting liver kinase B1. We thus demonstrated that nesfatin-1 treatment at appropriate doses suppressed arterial remodeling without affecting blood pressure. Our findings indicate that nesfatin-1 can be a therapeutic target for improved treatment of peripheral artery disease.