Comprehensive Analysis of the Prognostic Marker and Immune Infiltrates of LDLR-Related Proteins Family Members in Breast Cancer.

Background & Objective: Breast cancer (BC) is one of the most frequent tumors worldwide, accounting for 15% of all cancer-related deaths. A timely diagnosis of BC is essential for optimal treatment and increasing patients' survival rates. LRP family proteins are important components of cell-surface receptors involved in numerous biological activities. Expression of LRP is related to breast malignancy. In this study, we initially studied the expression of LRPs in BC tissues compared to normal tissues-the relation of LRP expression with relapse-free survival (RFS) and overall survival (OS). Then, we investigated the association of LRPs relation and immune infiltrating abundance. Methods: We analyzed the LDLR family expression and prognostic value in BC by mining UALCAN, TIMER, and Kaplan-Meier plotter databases. Subsequently, we explored the association of LDLR expression and immune infiltrating abundance via the TIMER database. Results: Expression levels of LRP1/2/4/9/10 were found to be higher in the cases with positive estrogen receptors. There was a positive association between LRP1/6 expression and the infiltration of CD8+ T cells, CD4+ T Cell, Macrophage, Dendritic Cell, and Neutrophil. Conclusion: Our study recommends LDLR as a potential prognostic biomarker that can be promising to improve the survival of BC patients' survival. However, further investigations are needed to evaluate the studied LDLR members in more detail.

Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review.

Background: Diabetes mellitus (DM) is a category of metabolic conditions affecting about 5% of people worldwide. High mortality associated with DM is mostly due to its severe clinical complications, including diabetic nephropathy, retinopathy, neuropathy, and cardiomyopathy. Resveratrol (RSV) is a natural, biologically active polyphenol known to have various health-promoting effects in animal models and humans. Objective: In this review, we have reviewed the preventive and therapeutic role of RSV on diabetes complications with emphasis on its molecular mechanisms of action. Methods: To prepare this review, all the basic and clinical available literatures regarding this topic were gathered through electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar. Therefore, we summarized previous studies that have evaluated the effects of RSV on diabetic complications and their mechanisms. Only English language studies published up to January 2023 were included in this review. Results: RSV improves glucose homeostasis, decreases insulin resistance, induces autophagy, regulates lipid metabolism, protects pancreatic ß-cells, ameliorates metabolic disorders, and increases the GLUT4 expression. These effects induced by RSV are strongly associated with ability of this polyphenol agent to elevation expression/activity of AMP-activated protein kinase and Sirtuin 1 in various organs of diabetic subjects, which leads to prevention and therapy of diabetic complications. In addition, antioxidant and anti-inflammatory properties of RSV were reported to be involved in its action in diabetic complications, such as retinopathy and nephropathy. Conclusion: RSV is a promising compound for improving diabetic complications. However, the exact antidiabetic mechanisms of RSV need to be further investigated.

Cell Therapies and Gene Therapy for Diabetes: Current Progress.

The epidemic of diabetes continues to be an increasing problem, and there is a need for new therapeutic strategies. There are several promising drugs and molecules in synthetic medicinal chemistry that are developing for diabetes. In addition to this approach, extensive studies with gene and cell therapies are being conducted. Gene therapy is an existing approach in treating several diseases, such as cancer, autoimmune diseases, heart disease and diabetes. Several reports have also suggested that stem cells have the differentiation capability to functional pancreatic beta cell development in vitro and in vivo, with the utility to treat diabetes and prevent the progression of diabetes-related complications. In this current review, we have focused on the different types of cell therapies and vector-based gene therapy in treating or preventing diabetes.

Comprehensive Analysis of the Expression, Prognosis, and Immune Infiltrates for Chromodomain-Helicase-DNA-Binding Proteins in Breast Tumor.

BACKGROUND: Several recent studies suggest that chromodomain-helicase -DNA-binding domains (CHDs) are linked with cancers. We explored the association between chromodomain-Helicase-DNA-binding domain proteins and breast cancer (BrCa) and introduced potential prognostic markers using various databases. MATERIALS AND METHODS: We analyzed the expression of the CHD family and their prognostic value in BrCa by mining UALCAN, TIMER, and Kaplan-Meier plotter databases. The association of CHD expression and immune infiltrating abundance was studied via the TIMER database. In addition, microRNAs related to the CHD family were identified by using the MirTarBase online database. RESULTS: The present study indicated that compared to normal tissues, BrCa tissues showed increased mRNA levels of CHD3/4/7 but decreased CHD2/5/9 expression. Interestingly, We also found a positive correlation between CHD gene expression and the infiltration of macrophage, neutrophil, and dendritic cells in BrCa, except CHD3/5. The Kaplan-Meier Plotter analysis suggested that high expression levels of CHD1/2/3/4/6/8/9 were significantly related to shorter relapse-free survival (RFS), while higher mRNA expression of CHD1, CHD2, CHD8, and CHD9 was significantly associated with longer overall survival of BrCa patients. The miRNAs of hsa-miR-615-3p and hsa-let-7b-5p were identified as being more correlated with the CHD family. CONCLUSION: The altered expression of some CHD members was significantly related to clinical cancer outcomes, and CHD1/2/8/9 could serve as potential prognostic biomarkers to improve the survival of BrCa patients. However, to evaluate the studied CHD members in detail are needed further investigations including experimental validation.

Curcumin as a regulator of Th17 cells: Unveiling the mechanisms.

Curcumin, a polyphenol natural product derived from turmeric, possesses diverse pharmacological effects due to its interactions with various cells and molecules. Recent studies have highlighted its immunomodulatory properties, including its impact on immune cells and mediators involved in immune responses. Th17 cells play a crucial role in promoting immune responses against extracellular pathogens by recruiting neutrophils and inducing inflammation. These cells produce inflammatory cytokines such as TNF-α, IL-21, IL-17A, IL-23, IL-17F, IL-22, and IL-26. Curcumin has been shown to significantly inhibit the proliferation of Th17 cells and reduce the production of inflammatory cytokines, including TNF-α, IL-22, and IL-17. This review aims to assess the effectiveness of curcumin and its underlying mechanisms in modulating Th17 cells.

RNA interference-based therapies for atherosclerosis: Recent advances and future prospects.

Atherosclerosis represents a pathological state that affects the arterial system of the organism. This chronic, progressive condition is typified by the accumulation of atheroma within arterial walls. Modulation of RNA molecules through RNA-based therapies has expanded the range of therapeutic options available for neurodegenerative diseases, infectious diseases, cancer, and, more recently, cardiovascular disease (CVD). Presently, microRNAs and small interfering RNAs (siRNAs) are the most widely employed therapeutic strategies for targeting RNA molecules, and for regulating gene expression and protein production. Nevertheless, for these agents to be developed into effective medications, various obstacles must be overcome, including inadequate binding affinity, instability, challenges of delivering to the tissues, immunogenicity, and off-target toxicity. In this comprehensive review, we discuss in detail the current state of RNA interference (RNAi)-based therapies.

Monkeypox: Virology, laboratory diagnosis and therapeutic approach.

Monkeypox infection outbreaks have been observed sporadically in Africa, usually as a result of interaction with wildlife reservoirs. The genomes of the new strain range in size from 184.7 to 198.0 kb and are identified with 143-214 open reading frames. Viral cores are rapidly carried on microtubules away from the cell's perimeter and deeper into the cytoplasm once the virus and cell membranes fuse. Depending on the kind of exposure, patients with monkeypox may experience a febrile prodrome 5-13 days after exposure, which frequently includes lymphadenopathy, malaise, headaches, and muscle aches. A different diagnostic approach is available for monkeypox, including histopathological analysis, electron microscopy, immunoassays, polymerase chain reaction, genome sequencing, microarrays, loop-mediated isothermal amplification technology and CRISPR (i.e., "clustered regularly interspaced short palindromic repeats"). There are currently no particular, clinically effective treatments available for the monkeypox virus. An initial treatment is cidofovir. As a monophosphate nucleotide analog, cidofovir is transformed into an inhibitor of viral DNA polymerase by cellular kinases, which is analogous to cidofovir's function in inhibiting viral DNA synthesis. The European Medicine Agency and the Food and Drug Administration have both granted permission for IMVAMUNE, a replication-deficient, attenuated third-generation modified vaccinia Ankara vaccine, to be used for the prevention of smallpox and monkeypox in adults.

Effect of CDH1 and CDH2 genes polymorphisms in oral squamous cell carcinoma susceptibility in a sample of Iranian population: A case-control study.

Background and Aims: Oral squamous cell carcinoma (OSCC) is a global malignant epithelial neoplasm affecting the oral cavity. Cadherins, as an adhesion molecule, are involved in cell-cell interaction. We aim to study the effect of two cadherin polymorphisms on OSCC risk in southeast of Iran. Methods: In this case-control study, 94 individuals (47 OSCC cases and 47 controls), that referred to the Department of Oral Pathology, Faculty of Dentistry, Zahedan University of Medical Sciences, Iran were included. Cadherin single nucleotide polymorphisms CDH1 (rs16260) and CDH2 (rs11564299) were genotyped by the tetra-Amplification Refractory Mutation System-PCR technique. Results: N-cadherin genotyping showed that the AA, AG, and AG + GG were presented 78.7%, 17%, 21.3% versus 66%, 29.7%, 34% in the cases and the control group, respectively. AG genotype was more common in control than case (OR = 0.47, 95% CI: 0.17-1.29, p = 0.14). G allele was more prevalent in control (19.1%) than the case group (12.8%) (OR = 0.61, 95% CI: 0.27-1.36, p = 0.23). In E-cadherin, AC, AA, and AC + AA genotypes frequency were 17%, 12.8%, and 29.8% in case versus 8.5%, 8.5%, and 17% in the control group. Allele A was more common in the case than the control group (OR = 1.84, 95% CI: 0.84-4.03, p = 0.12). Also, AA and CC, the codominant genotypes were common in CDH2 and CDH1 respectively in all histopathological grades, and no statically significant association was observed between OSCC different histopathological grades and cadherin genotypes (p = 0.39 in N-cadherin, p = 0.74 in E-cadherin). Conclusion: Our results showed a lack of association between CDH1 and CDH2 gene polymorphisms with OSCC risk in a population of Southeastern of Iran.

A Deletion in Duchenne Muscular Dystrophy Gene Found Through Whole Exome Sequencing in Iran.

Duchenne muscular dystrophy (DMD) is a severe progressive X-linked neuromuscular illness that affects movement through mutations in dystrophin gene. The mutation leads to insufficient, lack of, or dysfunction of dystrophin. The cause of DMD was determined in an Iranian family. Exome sequencing was carried out along with a complete physical examination of the family. In silico methods were applied to find the alteration in the protein structure. The homozygous variant in DMD gene (NM-004006.2) was defined as c.2732-2733delTT (p.Phe911CysfsX8) in exon 21. In addition, phylogenetic conservation study of the human dystrophin protein sequence revealed that phenylalanine 911 is one of the evolutionarily conserved amino acids. In conclusion, our study indicated a new deletion in the DMD gene in the affected family. This deletion with an X-linked inheritance pattern is new in Iran. These findings could facilitate genetic counseling for this family and other patients in the future.

Gene and cell therapy approaches for familial hypercholesterolemia: An update.

Familial hypercholesterolemia (FH) is a common autosomal codominant hereditary illness marked by the heightened risk of early atherosclerotic cardiovascular disease and high blood levels of low-density lipoprotein cholesterol (LDL-C). FH patients can have homozygous or heterozygous variants. This condition has been linked to variations in the genes for the LDL receptor (LDLR), apolipoprotein B, proprotein convertase subtilisin/Kexin 9 (PCSK9), and LDLR adaptor protein 1. Drugs such as statins, ezetimibe, and PCSK9 inhibitors are currently widely available, allowing for the theoretical normalization of plasma LDL-C levels mostly in patients with heterozygous FH. However, homozygous FH patients usually have a poor response to traditional lipid-lowering therapy and may have a poor prognosis at a young age. LDL apheresis and novel pharmacological therapies such as microsomal transfer protein inhibitors or anti-angiopoietin-like protein 3 monoclonal antibodies are extremely expensive and unavailable in most regions of the world. Therefore, the unmet need persists for these patients. In this review, we discuss the numerous gene delivery, gene editing, and stem cell manipulation techniques used in this study to correct FH-causing LDLR gene variations in vitro, ex vivo, and in vivo. Finally, we looked at a variety of studies that corrected genetic defects that caused FH using the ground-breaking clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology.

Evaluating the Relationship Between Antiphospholipid Antibodies and COVID-19 Severity.

Coronavirus 2 (COVID-19) has emerged as a new global pandemic, causing severe acute respiratory syndrome. Furthermore, the existence of antiphospholipid (APL) antibodies (Abs) and ultimately patient death may be linked to the occurrence of thrombotic events in patients with COVID-19. We aimed to investigate if there was a link between the presence of APL Abs and the severity of COVID-19 disease in patients at the Vali-Asr Hospital in Zanjan from June to July 2021. Real-time PCR was used to diagnose COVID-19 in 76 hospitalized patients. A total of 38 patients were hospitalized in the internal medicine ward and another 38 people were admitted to the intensive care unit of the Vali-Asr Educational Hospital in Iran's Zanjan region. Lupus anticoagulant (LAC) detection was done using the dilute Russell viper venom time method, and tests for anticardiolipin (ACL) Abs, IgG and IgM, and anti-beta2 glycoprotein 1 Abs, IgG and IgM, were done on blood and plasma samples of linked patients using the enzyme-linked immunosorbent assay technique. SPSS 24 was used to analyze data. Our findings showed that the presence of LAC was associated with disease severity in COVID-19 patients (p = 0.001). However, there was no significant relationship between APL Abs and mortality in patients affected with COVID-19. The evaluation of APL Abs, particularly LAC, in COVID-19 patients appears to be helpful in predicting the severity of the disease.

Vitamin D role in hepatitis B: focus on immune system and genetics mechanism.

According to the World Health Organization (WHO) report, viral hepatitis has been a problem in human society. Vitamins play a significant role in preventing the hepatocarcinoma and liver cirrhosis. In this report, we will first focus on the vitamin D function in the immune system reactions, and then investigate its role in the viral infections and the signaling pathway of hepatitis B virus. The existence of the cytochrome P450 (CYP) 27B1 enzyme, which is involved in vitamin D synthesis in immune system cells, has drawn researchers ' attention to the field of immune system. Toll like receptor (TLR) play a significant role in the immune system, and are one of the primary receptors of the innate immune system. In addition, the synthesis of inflammatory cytokines, such as Interferon γ (IFNγ) and Interleukin-2 (IL-2) is one of the key roles of T helper type 1 (Th1) cells; these cells can suppress two cited cytokines via vitamin D. In the chronic phase of hepatitis B, Cytotoxic T lymphocytes (CTLs) cells have weaker performance than the acute phase of the disease. The association between vitamin D physiologies with viral infections is also confirmed by genetic studies, carried out on genetic variations of vitamin D receptor (VDR) R-encoding disease susceptibility gene. Vitamin D affects different phases of the disease. Therefore, further experiments in this area are proposed.

Protective effects of curcumin on ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is a term used to describe phenomena connected to the dysfunction of various tissue damage due to reperfusion after ischemic injury. While I/R may result in systemic inflammatory response syndrome or multiple organ dysfunction syndrome, there is still a long way to improve therapeutic outcomes. A number of cellular metabolic and ultrastructural alterations occur by prolonged ischemia. Ischemia increases the expression of proinflammatory gene products and bioactive substances within the endothelium, such as cytokines, leukocytes, and adhesion molecules, even as suppressing the expression of other "protective" gene products and substances, such as thrombomodulin and constitutive nitric oxide synthase (e.g., prostacyclin, nitric oxide [NO]). Curcumin is the primary phenolic pigment derived from turmeric, the powdered rhizome of Curcuma longa. Numerous studies have shown that curcumin has strong antiinflammatory and antioxidant characteristics. It also prevents lipid peroxidation and scavenges free radicals like superoxide anion, singlet oxygen, NO, and hydroxyl. In our study, we highlight the mechanisms of protective effects of curcumin against I/R injury in various organs.

Potential of MicroRNAs As Biomarkers and Therapeutic Targets in Respiratory Viruses: A Literature Review.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression through recognition of cognate sequences and interference of transcriptional, translational, or epigenetic processes. Hundreds of miRNA genes have been found in diverse viruses, and many of these are phylogenetically conserved. Respiratory viruses are the most frequent causative agents of disease in humans, with a significant impact on morbidity and mortality worldwide. Recently, the role of miRNAs in respiratory viral gene regulation, as well as host gene regulation during disease progression, has become a field of interest. This review highlighted the importance of various miRNAs and their potential role in fighting with respiratory viruses as therapeutic molecules with a focus on COVID-19.

Young woman with hypophosphatasia: A case report.

Hypophosphatasia is a rare inherited disease defined by teeth and bone mineralization impairment leading to depletion of tissue non-specific alkaline phosphatase. We define a young woman diagnosed with hypophosphatasia (after several times alkaline phosphatase levels were low) was discovered following femoral fracture. A 30-year-old woman who presented for a history of early permanent teeth loss during the last 5 years and HPP-like symptoms in family history and bone radiograph verified bowing, deficient mineralization, and symmetrical subtrochanteric stress fractures of femurs was referred to our clinic for further management. Blood test findings defined raised phosphorus levels on two occasions at 6.2 and 5.7 mg/dl and insufficient 25-hydroxy vitamin D level. HPP early diagnosis and adequate treatment, depending on the clinical symptoms along with laboratory tests, could be effective in decreasing the suffering of the disease and side effects.

Serum cortisol concentration and COVID-19 severity: a systematic review and meta-analysis.

The novel COVID-19 outbreak is a major health threat to human beings with multiorgan injuries. However, its endocrine system manifestations are much less studied. In this study, we aimed to reassess the available findings on the association between cortisol level and severity of COVID-19 infection. We conducted a systematic search on Medline/PubMed, Scopus, Web of Science, and Cochrane Library databases. To pool data, a random-effects model was performed depending on the heterogeneity among studies. Sensitivity analysis was also carried out by removing each study systematically. In addition, subgroup and meta-regression analyses were performed depending on the presence of the variables of sex and age. Subsequently, 11 studies (5 observational studies and 6 case reports) were included in the meta-analysis. Pooled analysis on the observational studies showed significantly higher levels of cortisol in patients with severe COVID-19 in comparison with those with mild-to-moderate COVID-19 (standardized mean difference: 1.48 µg/dL; 95% CI (0.51 to 2.46); p=0.003). Assessment of the results of case reports revealed that the patients with severe COVID-19 demonstrated higher cortisol levels than the patients with mild-to-moderate COVID-19. No publication bias was observed using the Begg's (p=0.08) and Egger's tests (p=0.09). Meta-regression illustrated a significant correlation between cortisol levels with sex. The serum cortisol level seems to be higher in patients with severe COVID-19 infection. This finding could be helpful to detect patients with poor prognosis at early stages of the disease, although age and sex may modify this level.

Neurological manifestations of coronavirus infections: role of angiotensin-converting enzyme 2 in COVID-19.

AIM OF THE STUDY: In December 2019, a highly pathogenic coronavirus called SARS-CoV-2 (formerly identified as 2019-nCoV) appeared in Wuhan, China, and has since been spreading rapidly around the world. we reviewed the neurological manifestations of this infection and the potential of ACE2 in the nervous system. MATERIALS AND METHODS: Six databases (Medline, Scopus, Embase, Web of Science, WHO, and google scholar) were searched and screened by the authors for having appropriate information about covid-19. Finally, 72 studies were identified, summarized and reviewed. RESULT: The most specific manifestation of SARS-CoV-2 patients is pulmonary distress, and several patients admitted to intensive care units were not able to breathe spontaneously. In addition, the SARS-CoV-2 outbreak has a significant effect on nervous systems and may even lead to serious neurological damage. The neuroinvasive pathobiology is still not fully elucidated and thus the effect of CoV infections on the nervous system needs to be explored. The spike protein of the virus and the angiotensin-converting enzyme 2 (ACE2) lead to the presence of both SARS-CoV and SARS-CoV-2 in the cells and, subsequently, decreased ACE2 expression. CONCLUSION: The therapeutic possibilities of ACE2 antibody, ACE2-derived peptides, and small molecule blockers of ACE2 include a receptor-binding domain blocking approach. Hence, future studies of ACE2 may be very helpful in discovering a therapy for SARS-CoV-2.

Prenatal stress and increased susceptibility to anxiety-like behaviors: role of neuroinflammation and balance between GABAergic and glutamatergic transmission.

Neuroplasticity during the prenatal period allows neurons to regenerate anatomically and functionally for re-programming the brain development. During this critical period of fetal programming, the fetus phenotype can change in accordance with environmental stimuli such as stress exposure. Prenatal stress (PS) can exert important effects on brain development and result in permanent alterations with long-lasting consequences on the physiology and behavior of the offspring later in life. Neuroinflammation, as well as GABAergic and glutamatergic dysfunctions, has been implicated as potential mediators of behavioral consequences of PS. Hyperexcitation, due to enhanced excitatory transmission or reduced inhibitory transmission, can promote anxiety. Alterations of the GABAergic and/or glutamatergic signaling during fetal development lead to a severe excitatory/inhibitory imbalance in neuronal circuits, a condition that may account for PS-precipitated anxiety-like behaviors. This review summarizes experimental evidence linking PS to an elevated risk to anxiety-like behaviors and interprets the role of the neuroinflammation and alterations of the brain GABAergic and glutamatergic transmission in this phenomenon. We hypothesize this is an imbalance in GABAergic and glutamatergic circuits (as a direct or indirect consequence of neuroinflammation), which at least partially contributes to PS-precipitated anxiety-like behaviors and primes the brain to be vulnerable to anxiety disorders. Therefore, pharmacological interventions with anti-inflammatory activities and with regulatory effects on the excitatory/inhibitory balance can be attributed to the novel therapeutic target for anxiety disorders.

Resveratrol and endothelial function: A literature review.

Endothelial dysfunction is a major contributing factor to diseases such as atherosclerosis, diabetes mellitus, obesity, hypertension, acute lung injury, preeclampsia, among others. Resveratrol (RSV) is a naturally occurring bioactive polyphenol found in grapes and red wine. According to experimental studies, RSV modulates several events involved in endothelial dysfunction such as impaired vasorelaxation, eNOS uncoupling, leukocyte adhesion, endothelial senescence, and endothelial mesenchymal transition. The endothelial protective effects of RSV are found to be mediated by numerous molecular targets (e.g. Silent Information Regulator 1 (SIRT1), 5' AMP-activated protein kinase (AMPK), endothelial nitric oxide synthase (eNOS), nuclear factor-erythroid-derived 2-related factor-2 (Nrf2), peroxisome proliferator-activated receptor (PPAR), Krüppel-like factor-2 (KLF2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)). Herein, we present an updated review addressing pharmacological effects and molecular targets of RSV in maintaining endothelial function, and the potential of this phytochemical for endothelial dysfunction-associated disorders.

Effect of orally-administrated thymoquinone during pregnancy on litter size, pentylenetetrazol-induced seizure, and body weight in rat offspring.

OBJECTIVES: This study aimed to assess the impact of orally-administrated thymoquinone (TQ) during pregnancy on litter size, pentylenetetrazol-induced seizure, and body weight in rat offspring. MATERIALS AND METHODS: In this experimental study, 64 pregnant rats were divided into groups according to the doses of TQ (0,10, 40, and 80 mg/kg) and gestational week (GW2 and GW3) of TQ administration. After parturition, the pups were counted, weighed, and assessed for pentylenetetrazol (PTZ)-induced seizure on postnatal days 14 (P14) and 21 (P21). RESULTS: In GW2 treated rats, TQ 40 mg/kg decreased seizure stages compared with control only on P14 while seizure duration significantly decreased on P14 and P21. On P14, 40 mg/kg TQ increased latency to the first seizure but decreased it on P21. In addition, 40 mg/kg dose decreased body weight (BW) on P1, P14, and P21 compared with 10 mg/kg dose and control groups. The dose of 80 mg/kg led to a complete pregnancy loss. In GW3 treated rats, only 10 mg/kg TQ decreased the seizure stages on P14 and P21. None of the doses had a significant effect on seizure duration and latency. TQ 40 and 80 mg/kg led to a low birth weight while increased BW on P14 and P21. A 50% decrease in litter size was observed in 80 mg/kg treated rats. CONCLUSION: Prenatal TQ may have anticonvulsant effects. The effects of TQ on BW of offspring depend on its dose and administration time. Also, a high dose of TQ at GW2 can be severely toxic for pregnancy.