Search Results (67)

Background/Objectives: Minipuberty represents the second phase of physiological activation of the reproductive axis and may play a role in postnatal genital development. Its course has been shown to be affected by untreated or inadequately treated maternal hypothyroidism. The aim of the present study was to investigate minipuberty in the sons of women with euthyroid autoimmune thyroiditis during pregnancy. Methods: This prospective matched cohort study included three groups of apparently healthy infant boys. Two groups comprised the male offspring of levothyroxine-naive, euthyroid women with autoimmune thyroiditis: one group was unsupplemented, and the other received vitamin D and selenium supplementation. The control group consisted of boys born to healthy women. Salivary concentrations of testosterone, androstenedione, DHEA-S, estradiol, and progesterone, along with urinary FSH and LH levels, were assessed longitudinally over the first 12 months of life. These hormonal measurements were evaluated in relation to genital development, including testicular volume and penile length, which were recorded at each study visit. Results: Compared with the offspring of healthy mothers, sons of women with autoimmune thyroiditis who did not receive supplementation exhibited lower concentrations of LH and testosterone, without a distinct peak, while the duration of hormone detectability did not differ between the groups. These hormonal alterations were accompanied by reduced penile length, with no differences observed in testicular volume. This group also exhibited lower DHEA-S concentrations, whereas levels of other hormones were comparable. In contrast, in the group receiving vitamin D and selenium supplementation, the dynamics of hormonal changes and genital organ growth did not differ from those observed in the control group. LH concentrations were inversely correlated with thyroid peroxidase antibody titers, which were lower in the supplemented group. Conclusions: The findings indicate an altered course of minipuberty in the sons of women with euthyroid autoimmune thyroiditis during pregnancy and suggest a potential benefit of exogenous vitamin D and selenium supplementation in this population. Full article

Background/Objectives: Minipuberty is a transient activation of the hypothalamic–pituitary–gonadal axis in infancy that contributes to the postnatal development of sexual organs. Its course has been shown to be influenced by maternal hypothyroidism. This study aimed to evaluate the reproductive axis and genital development in infant girls born to women with euthyroid autoimmune thyroiditis. Methods: The study involved three groups of infants: two groups were daughters of euthyroid women with autoimmune thyroiditis, while the third group (control) consisted of daughters of women without thyroid disease during pregnancy. Half of the mothers with thyroiditis received additional vitamin D and selenium supplementation during pregnancy, whereas the other half did not. During the first 18 months of life, periodic assessments were conducted of gonadotropin concentrations in urine, as well as salivary levels of estradiol, progesterone, testosterone, androstenedione, and DHEA-S. Additionally, ovarian volume, uterine length, and breast diameter were measured in the infants. Results: Daughters of women with autoimmune thyroiditis who did not receive supplementation during pregnancy exhibited lower levels of LH, estradiol, and progesterone, as well as a more rapid decline in LH and estradiol to below detectable levels, compared with daughters of healthy women. These hormonal differences were accompanied by smaller uterine length and breast diameter in this group. No differences were observed between the offspring of non-supplemented women with thyroiditis and daughters of healthy women regarding the levels of other hormones or ovarian volume. The dynamics of all assessed hormone levels and organ measurements did not differ between daughters of euthyroid women with thyroiditis who received vitamin D and selenium supplementation and daughters of healthy women. LH and progesterone levels showed inverse correlations with anti-thyroid peroxidase antibody titers, whereas uterine and breast dimensions positively correlated with estradiol levels. Conclusions: These findings suggest that maternal euthyroid autoimmune thyroiditis can affect the progression of female minipuberty, while supplementation with vitamin D and selenium during pregnancy may mitigate this effect. Full article

Toll-like receptors (TLRs) are conserved pattern recognition receptors essential to insect innate immunity. However, the functions of TLRs in Loxostege sticticalis, a destructive agricultural pest, remain poorly characterized. In this study, the full-length coding sequence of the L. sticticalis Toll receptor (LsToll) was identified and characterized to analyze its molecular features. Structural analysis showed that LsToll possesses typical Toll family features, including an extracellular domain containing 19 leucine-rich repeats (LRRs), a transmembrane helix, and a highly conserved intracellular Toll/interleukin-1 receptor (TIR) domain. LsToll transcript levels were significantly upregulated after bacterial challenge. RNAi-mediated silencing of LsToll significantly reduced larval tolerance to bacterial infection and increased mortality. Notably, LsToll suppression also induced severe developmental abnormalities, including molting obstruction, pupation failure, and defects in wing expansion in newly emerged adults. Transcriptome analysis after RNAi identified 5230 differentially expressed genes (DEGs), which were significantly enriched in insect hormone biosynthesis and metabolic pathways. Biochemical assays further confirmed that LsToll knockdown decreased 20-hydroxyecdysone (20E) titers and increased juvenile hormone III (JH III) titers. These results suggest that LsToll contributes to antibacterial defense and normal development in L. sticticalis. Its involvement in both survival and development indicates that LsToll may serve as a promising molecular target for sustainable pest management strategies. Full article

Dendroctonus valens LeConte represents a major invasive pest species in China. Both larvae and adults primarily feed on the phloem of the tree trunk base and roots, disrupting nutrient transport and leading to host tree mortality, which poses a severe threat to forest ecosystems and the forestry economy. Juvenile hormone acid methyltransferase (JHAMT) is a key enzyme in insect juvenile hormone (JH) biosynthesis. In this study, we identified a JHAMT-encoding gene, DvJHAMT, in D. valens via bioinformatic analysis. RT-qPCR analysis revealed that DvJHAMT is predominantly expressed during the egg and larval stages. In the fourth-instar larvae, the highest expression levels were observed in the head and epidermis, suggesting a central regulatory role during this critical developmental period. To investigate its function via RNA interference (RNAi), a nanomaterial, star polycation (SPc), was employed for the transdermal delivery of dsRNA into the fourth-instar larvae. The results demonstrated that DvJHAMT knockdown significantly downregulated mRNA levels, resulting in marked decreases in larval survival, pupation, and eclosion rates. Notably, treatment with 0.7 µg dsDvJHAMT-SPc resulted in a 96.67% mortality rate and a reduced pupation rate of 41.67% at 34 days post-treatment. Furthermore, RNAi led to developmental deformities and significant weight loss in larvae. ELISA assays confirmed that DvJHAMT silencing led to reduced JHAMT enzyme activity and JH III titers in a dose-dependent manner. In conclusion, our findings demonstrate that DvJHAMT plays a vital role in JH biosynthesis and that its suppression exhibits potent lethal effects, suggesting that DvJHAMT is a promising candidate for RNAi-based management of D. valens. Full article

Honeybees play a vital role in pollinating crops and wild plants, but their health and efficiency are strongly influenced by their body size. Large bees tend to have longer lifespans, stronger foraging abilities, and greater resistance to diseases. However, the molecular mechanisms that control honeybees’ body size are not fully understood. In this study, we focused on 3 to 5-day-old larvae of Apis mellifera ligustica and investigated the roles and interactions of juvenile hormone (JH), juvenile hormone esterase (JHE), and TITIN in regulating honeybees’ body size using RNAi, exogenous hormone treatment, and qRT-PCR. The results showed that suppression of Jhe expression caused JH accumulation in larvae, subsequently reducing Titin expression and ultimately increasing adult body size. Furthermore, exogenous application of JHIII also inhibited the expression of Titin. Suppression of Titin expression alone directly increased the body size of adult honeybees, but did not affect the JH titer, which indicates that JH negatively regulates Titin expression in a unidirectional manner, whereas Titin does not feedback-regulate JH titer. The study suggests a regulatory link between JH, Jhe, and Titin in body size control. The discovery of this pathway, when combined with traditional breeding methods, may provide insights for future breeding strategies in honeybees. Full article

Oxidative stress appears to be implicated in both the initiation and progression of autoimmune thyroiditis. Selenomethionine, which exhibits antioxidant properties, has been shown to reduce thyroid antibody titers in patients with autoimmune thyroiditis. Recent evidence suggests that vitamin E, a fat-soluble antioxidant, may protect against the development of autoimmune thyroiditis, and that its supplementation has been associated with improvements in female sexual function. The objective of the present pilot study was to determine whether vitamin E intake modulates the effects of selenomethionine on female sexual function and depressive symptoms in individuals with thyroid autoimmunity. The study enrolled three groups of reproductive-age women with euthyroid autoimmune thyroiditis, with 26 participants in each group. The groups were matched for age, thyroid peroxidase antibody titers, and TSH levels and differed according to vitamin E intake: adequate intake (group A), low intake (group B), and high intake (group C). All participants received selenomethionine supplementation (200 µg/day) for six months. Antibody titers and hormone levels were measured, and participants completed questionnaires assessing female sexual function (FSFI) and depressive symptoms (BDI-II). At baseline, no differences in biochemical outcomes were observed between the groups, except for testosterone levels. The study groups differed in sexual desire and arousal domain scores, which were higher in group A than in the other two groups. Total FSFI scores, the remaining FSFI domain scores, and BDI-II scores did not differ between groups at baseline. Across all groups, selenomethionine reduced thyroid peroxidase and thyroglobulin antibody titers and increased SPINA-GD and the ratio of free triiodothyronine to free thyroxine; however, the effects on antibody titers were most pronounced in group A. An increase in SPINA-GT and testosterone levels following selenomethionine supplementation was observed only in group A. In this group, selenomethionine also led to significant improvements in total FSFI scores and all individual domain scores. In contrast, in the remaining groups, the effects of supplementation were limited to increases in domain scores for lubrication, sexual satisfaction, and pain. A treatment-related reduction in total BDI-II scores was observed exclusively in women with adequate vitamin E intake. These findings suggest, for the first time, that dietary intake of a natural antioxidant may influence the effects of exogenous selenomethionine on sexual function and depressive symptoms in reproductive-age women with euthyroid autoimmune thyroiditis. Full article

Thyroid disorders are among the most common endocrine disorders worldwide and are classified as noncommunicable diseases. These disorders are associated with significant morbidity, impaired quality of life, and considerable socioeconomic burden. Like other noncommunicable diseases, thyroid disorders arise from complex interactions between genetic susceptibility and environmental factors, including diet and lifestyle. Despite growing interest in lifestyle-based approaches to noncommunicable disease prevention and management, thyroid disorders have received comparatively limited attention in this context. Graves’ disease, the most common cause of hyperthyroidism, is a relevant condition for exploring dietary interventions. Current treatment strategies—anti-thyroid drugs, radioactive iodine and thyroidectomy—have remained largely unchanged for decades. Long-term remission following drug therapy is achieved in no more than approximately 50% of patients, while all treatment modalities carry potential adverse effects. These limitations underscore the need for alternative or adjunctive therapeutic strategies. Iodine intake plays a central role in thyroid hormone synthesis. Indeed, observational studies have shown inverse associations between iodine intake and remission rates, as well as achievement of euthyroidism, medication requirements and thyroid autoantibody titers. These findings suggest that dietary iodine restriction may enhance treatment efficacy and reduce medication-related risks. Beyond its direct effects on thyroid hormone synthesis, iodine may influence Graves’ disease through indirect mechanisms involving the lipid profile and the gut–thyroid axis. Autoimmune thyroid diseases are associated with a dyslipidemic profile and with gut microbiota dysbiosis; the latter characterized by increased potentially pathogenic bacteria and reduced beneficial bacteria such as Lactobacillus and Bifidobacterium. Full article

Juvenile hormone (JH) is a key regulator of larval development in honeybees. Its biosynthesis involves multiple enzymatic steps and is modulated by a complex regulatory network that includes microRNAs (miRNAs). Juvenile hormone acid methyltransferase (JHAMT) catalyzes the final step in JH synthesis. This study demonstrates that the miRNA novel-m0027-3p negatively regulates the expression of the Jhamt gene in Apis mellifera larvae (AmJhamt), thereby mediating JH biosynthesis. Bioinformatics predictions indicate that novel-m0027-3p potentially targets six hormone-related genes (22 mRNAs), including AmJhamt. Dual-luciferase reporter assays and mimics/inhibitor-miRNA feeding confirmed that novel-m0027-3p significantly suppresses the expression of the target gene AmJhamt. In vivo experiments showed that larvae fed with the mimics of novel-m0027-3p exhibited decreased JH titers and significantly downregulated expression of JH signaling downstream genes AmHex70b and AmKr-h1. Conversely, larvae fed with the inhibitors of novel-m0027-3p displayed significantly elevated JH titers and markedly upregulated expression of AmHex70b and AmKr-h1. Our findings provide experimental evidence for the coupling between miRNAs and hormonal pathways in honeybees. Full article

Autoimmune thyroiditis (AIT) is characterized by dysregulated endocrine–immune interactions, and vitamin D has been proposed as a potential immunomodulatory factor influencing vaccine-induced immune responses. This study investigated the association between serum vitamin D status and humoral responses to SARS-CoV-2 vaccination in patients with AIT, while exploring potential molecular mechanisms using network pharmacology, molecular docking and Molecular Dynamics (MD) simulations. Patients were stratified according to serum 25-hydroxyvitamin D levels as deficient, insufficient, or sufficient. Anti–spike receptor-binding domain (RBD) IgG titers, thyroid autoantibodies, and thyroid-stimulating hormone levels were measured. In parallel, vitamin D₃ related molecular targets were integrated with AIT-associated genes, followed by protein–protein interaction analysis, molecular docking and MD simulations were performed to assess the interactions between vitamin D₃ (cholecalciferol) and selected key proteins. An inverse correlation was observed between serum vitamin D levels and anti-RBD IgG titers (p = 0.0013), with higher antibody responses detected in vitamin D-deficient patients. Network pharmacology analysis highlighted CYP19A1, CYP17A1, and ESR1 as prioritized targets associated with steroid hormone biosynthesis and endocrine signaling pathways. Molecular docking showed compatible binding of vitamin D₃ to these proteins, while MD simulations supported the structural stability of the complexes over time. Collectively, these findings suggest that vitamin D status may influence post-vaccination humoral immune responses in AIT, potentially through modulation of endocrine–immune crosstalk. Further longitudinal and mechanistic studies are required to clarify causality and clinical relevance. Full article

Insect insulin signaling plays a central role in regulating development, metamorphosis, and reproduction, yet its mechanistic functions in the tomato leafminer, Tuta absoluta, a globally significant pest, remain poorly understood. This study aimed to elucidate the role of the serine/threonine kinase Akt (TaAkt) in coordinating metamorphosis and female reproductive processes. The TaAkt gene was cloned and characterized, and its spatiotemporal expression was analyzed across various developmental stages and tissues. RNA interference (RNAi) was employed to knock down TaAkt in late pupae and newly emerged females, followed by assessment of pupal-adult eclosion, chitin metabolism, 20-hydroxyecdysone (20E) titer, ovarian development, juvenile hormone (JH) levels, vitellogenin synthesis, and fecundity. Knockdown of TaAkt significantly reduced 20E titers and downregulated the expression of ecdysone biosynthesis and signaling genes, leading to pupal mortality, defective molting, and reduced chitin content. In adult females, TaAkt silencing impaired ovarian growth, decreased JH levels, suppressed vitellogenin production, and reduced egg number and hatching rates. These findings demonstrate that TaAkt exerts pleiotropic control over both metamorphic and reproductive processes in T. absoluta. The study identifies TaAkt as a promising molecular target for RNAi-based pest management strategies, offering a potential approach to simultaneously suppress survival and reproductive capacity in this economically important pest. Full article

Background: The interplay between obesity and thyroid dysfunction is complex, characterized by adaptive hyperthyrotropinemia and peripheral hormone resistance. Metabolic and Bariatric surgery (MBS) has emerged not only as a weight-loss (WL) intervention but also as a potent modulator of the thyroid–gut axis. Methods: We conducted a narrative review of the literature (2015–2025), synthesizing data from prospective cohorts, meta-analyses, and mechanistic studies to evaluate the impact of MBS on thyroid function, autoimmune dynamics, and drug pharmacokinetics. Discussion: Current evidence suggests that MBS promotes a recalibration of the thyroid axis. Post-operative WL is independently associated with a significant reduction in serum thyroid-stimulating hormone (TSH) and free triiodothyronine (fT3) levels, reversing obesity-induced peripheral resistance. Concurrently, the reduction in systemic inflammation (NOD-like receptor protein 3 (NLRP3) inflammasome deactivation) may dampen lymphocytic infiltration, while the amelioration of gut dysbiosis and intestinal permeability is hypothesized to reduce cross-reactivity mechanisms (molecular mimicry), leading to decreased antibody titers in Hashimoto’s thyroiditis. However, these benefits are counterbalanced by altered drug absorption mechanisms. While most hypothyroid patients benefit from reduced Levothyroxine (L-T4) requirements due to decreased lean mass, malabsorptive procedures (Roux-en-Y Gastric Bypass, One Anastomosis Gastric Bypass) can precipitate refractory hypothyroidism due to bypassed absorptive surfaces and altered gastric pH. Conclusions: MBS offers a dual benefit of functional restoration and modulation of autoimmune markers. However, post-surgical management requires a tailored approach. Clinicians must distinguish between the physiological decline in TSH (adaptive) and iatrogenic malabsorption, advocating for liquid L-T4 formulations in complex malabsorptive phenotypes. Full article

Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and explores its potential metabolic implications in a high-prevalence region. Methods: In this comparative cross-sectional study adhering to STROBE guidelines, we enrolled 100 PCR-confirmed chronic HCV patients and 100 age/gender-matched controls from District Peshawar, Pakistan. Serum TSH, fT3, fT4, and anti-TPO antibodies were quantified. Multivariable logistic regression, adjusted for age, gender, and viral load, was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Thyroid dysfunction affected 41% of HCV patients vs. 12% of controls (aOR 5.2, 95% CI 2.8–9.6, p < 0.001), predominantly hypothyroidism (29% overall; 18% overt, 11% subclinical). Anti-TPO positivity was 38% in HCV vs. 8% in controls (aOR 6.7, 95% CI 3.1–14.5, p < 0.001). Anti-TPO titers correlated positively with TSH (r = +0.62, p < 0.001) and inversely with fT3/fT4. Subgroup analysis showed higher dysfunction in patients aged ≥40 years (52% vs. 28%, p = 0.012) and viral load ≥ 10⁶ IU/mL (48% vs. 32%, p = 0.041). We hypothesize that these findings may have significant metabolic implications, including impaired mitochondrial β-oxidation and insulin resistance. Conclusions: HCV infection is strongly associated with autoimmune hypothyroidism, which may amplify cardiometabolic risk. The paper has not explicitly identified metabolic parameters, including lipid profiles, indices of insulin resistance, and metabolomic signatures, and, therefore, any metabolic inferences are speculative and based on established thyroid and HCV pathophysiology. Routine thyroid screening pre- and post-DAA therapy is recommended, alongside metabolomic profiling to validate these proposed metabolic pathways. Full article

Background: Hashimoto’s thyroiditis (HT) is the result of a complex interplay between genetic, environmental, and epigenetic factors. The role of cellular and humoral immunity in the pathogenesis of the disease is well-established. Inflammatory infiltration of T and B lymphocytes is a key feature identified on ultrasound examination. The lack of data on the effect of L-thyroxine (LT-4) doses on the level of anti-TPO and anti-TG antibodies in Hashimoto’s thyroiditis and the relationship with anthropometric measurements resulted in the desire to fill this niche. Methods: A total of 70 Caucasian patients diagnosed with Hashimoto’s thyroiditis within the past two years were examined. The participants were divided into three groups based on their L-thyroxine dosage (≤50, 50–100, >100 μg). Results: The results revealed no correlation between the dosage of L-thyroxine and anthropometric measurements (age, height, body weight, and body fat content). No correlation was identified between the levels of anti-TPO and anti-TG and the dose of L-thyroxine in patients with Hashimoto’s thyroiditis. Conclusions: The mechanism regulating the levels of anti-TPO and anti-TG appears to be associated with a more advanced thyroid inflammation and disease process. Long-term observation of patients would be advisable. We present evidence of no effect of hormone dose on antibody levels in Hashimoto’s thyroiditis. Regardless of disease severity, immune regulation remains outside the scope of hormonal regulation. Full article

The development of novel control strategies for the major cowpea pest Megalurothrips usitatus requires a deeper understanding of its critical molecular regulators. The nuclear receptor Fushi-tarazu factor 1 (FTZ-F1) is a conserved master regulator of insect development and reproduction, yet its function in M. usitatus remains uncharacterized. In this study, we investigated the expression and functional role of MuFTZ-F1 in this pest. RT-qPCR analysis revealed ubiquitous MuFTZ-F1 expression across all developmental stages and in major adult tissues. RNA interference (RNAi)-mediated knockdown of MuFTZ-F1 in the 2nd instar nymphs caused severe developmental defects, including impaired eclosion and significantly increased mortality. Mechanistically, silencing led to a significant reduction in the molting hormone ecdysone, accounting for the observed molting arrest. Furthermore, MuFTZ-F1 knockdown significantly decreased dopamine titers in both nymphs and female adults, suggesting its involvement in regulating this key biogenic amine beyond developmental processes. Our results provide the first functional evidence that MuFTZ-F1 is indispensable for nymphal development and survival in M. usitatus, mediated through the regulation of ecdysone. The profound lethal effect of MuFTZ-F1 silencing underscores its promise as a target for RNAi-based pest management strategies against this economically important pest. Full article

Introduction: Vitamin D is involved in numerous processes and is obtained both exogenously and endogenously. Its active form is 1,25-dihydroxycholecalciferol, which exerts its biological effects via the vitamin D receptor (VDR). The main factors influencing VDR density are polymorphisms of the VDR gene, which may affect, e.g., gene mRNA stability and also VDR gene expression. There are four main polymorphic sites within the gene, BsmI, ApaI, FokI and TaqI, and two polymorphisms related to the gene promoter: GATA and Cdx2. One of the functions of vitamin D is to modulate the immune system. It affects T lymphocytes, B lymphocytes and dendritic cells. Currently, vitamin D deficiency is a common global problem that is associated with an increased risk of autoimmune diseases, including Hashimoto’s thyroiditis. Numerous studies have demonstrated an association between low vitamin D levels and elevated thyroid-stimulating hormone (TSH) levels, and have also proven the existence of a negative correlation between vitamin D levels andanti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibody titers. Review objectives and a concise summary of the methodology: The review aims to analyze studies examining the relationship between specific VDR polymorphisms, vitamin D levels, and the development of various diseases, with a particular emphasis on Hashimoto’s thyroiditis. This review is based on original and review articles written in English published between March 2018–November 2024 searched primarily in the PubMed, and additionally in Google Scholar databases. A narrative review of the literature was conducted. Conclusions: The presence of specific VDR polymorphisms influences the effectiveness of vitamin D supplementation, but the role of supplementation in the prevention of autoimmune diseases has not been definitively confirmed. To date, studies have primarily involved relatively small groups of patients with significant population heterogeneity, with case–control investigations being the most common. Therefore, further research on larger, more homogeneous groups is recommended to achieve more standardized results. Additionally, the influence of epigenetic factors modulating VDR activity and its interactions with the environmental factors is also important. Full article