Endocrine, metabolic & immune disorders drug targets最新文献

Aim: This study aimed to describe characteristics and treatment choices among AMABs (Assigned Male At Birth) and AFABs (Assigned Female At Birth) transgenders enrolled from March 2021 to July 2023 at the PTA S. Giorgio of the ASP3-Catania.

Case history: A total of 145 patients were studied, and there was no prevalence of AMAB/AFAB. At first observation for AMABs, the age was 26 years and 25 years for AFABs, with 11 AMAB/AFAB declared as "non-binary" (average age 17 years).

Results: In AMAB/AFAB, we evaluated hormonal treatment, efficacy, and dosage/hormonal levels. In AMABs, oral estradiol valerate (4 mg/day) or transdermal estradiol in gel (2 mg/day) + oral cyproterone acetate (25 mg/day) for both estrogenic formulations were used. Testosterone (TE), LH, FSH, and PRL at baseline and during chronic treatment were measured. In AFABs, we used injectable TE (250 mg/3-4 weeks or 1 g/12-16 weeks) or transdermal TE (60- 80 mg/day). In these patients, we analyzed blood count, LH, FSH, and TE. Hematocrit, hemoglobin, and red blood cell count showed a modest elevation after 4-6 months of treatment. About 32% of AFABs complained of transient uterine bleeding, but no hypertension or ovarian pathology was detected.

Conclusion: In AMABs, despite the short observation period, no patient showed an increased risk of myocardial infarction and ischemic stroke. Among AFABs, no increased risk of cardiovascular or cerebrovascular disease was observed. Furthermore, given the complexity of the phenomenon, the integration between the different professional figures who require specific and qualified skills is fundamental.

Introduction: Postprandial hypoglycemia induced by Dumping Syndrome (DS) represents a side effect of bariatric surgery linked to glucose-dependent hyperinsulinemia, which can cause serious symptoms 2-3 hours after the meal hypoglycemia. This clinical case shows the effectiveness of semaglutide, a long-acting GLP1 receptor agonist, in one patient previously subjected to gastric bypass (GBP), with persistent late postprandial hypoglycaemic symptoms occurring after surgery.

Case report: A female patient, 31 years old, subjected to GBP 10 years earlier, with the diagnosis of diabetes, was admitted to our unit for persistent post-prandial reactive hypoglycemia, confirmed by Flash Glucose Monitoring (FGM) FreeStyle. The patient was intolerant to metformin, had been treated with acarbose with poor results. HbA1c 7.9%. Acarbose was suspended, and semaglutide was started sc at increasing doses, 0.25 mg/week for 1 month and subsequently 0.5 mg/week. After the first few weeks, symptoms of DS were significantly reduced with improvement of the daily glycemic profile and disappearance of hypoglycemic events. The time-below range, time spent with blood glucose <70 mg/dl, decreased by 12% to 4% during treatment with semaglutide 0.25 mg/week, up to 1% with a dose of 0.5 mg/week. The effect of the drug on reducing hypoglycemic episodes was persistent for up to 8 months.

Conclusion: Treatment of post-bariatric reactive hypoglycemia includes nutritional therapy, the use of glucosidase inhibitors, and somatostatin analogues. The use of short-acting GLP-1RA analogues has also recently been reported. In our patient, therapy with semaglutide s.c. significantly reduced episodes of reactive hypoglycemia with an improvement in the quality of life.

Background: There is a lack of solid long-term evidence with respect to the management over time of adrenal incidentalomas that miss clearly benign radiological features. We present the case of a 75-year-old man with a non-secreting adrenal mass, apparently stable in size (14 mm) and unchanged in features for 2 years, but subsequently diagnosed as adrenal carcinoma.

Case report: The patient was referred to Grande Ospedale Metropolitano Niguarda in August 2022 due to the presence of a large lesion in the left adrenal site. In 2017, a 14 mm, 20 HU, round, regular-edged lesion was detected at a CT scan without contrast medium. Over the next two years, the patient was re-evaluated every 6 months with follow-up CT scans with no apparent densitometric or dimensional changes in the known lesion. In September 2022, 3 years after the last CT scan, the patient was hospitalised for pneumonia. An abdominal CT scan acquired during the hospitalisation showed an increase of the lesion to 14.5x10x12 cm. The patient subsequently underwent open nephrosurrenectomy, and histological examination confirmed the presence of an adrenal carcinoma (proliferation index 5%, Weiss score 7). No adjuvant therapy was administered, and the last CT scan in December 2022 was negative for the recurrence of the disease.

Conclusion: Adrenal carcinoma usually presents as a clearly malignant lesion with rapid growth and a marked tendency to metastasise. This case highlights how an adrenal adenoma with indeterminate features is worthy of follow-up over time despite its apparent dimensional and radiological stability [1].

Background: Schmidt's syndrome (SS) is a subtype of polyglandular autoimmune syndrome type-2 combining autoimmune thyroiditis (AIT) and autoimmune Addison's disease (aAD). It occurs most frequently in young adult females, and aAD is the most common initial manifestation [1]. We present a rare case of SS with late-onset aAD and severe hyponatremia as the first sign.

Case report: A 73-year-old woman presented to the emergency department (ED) with a 10-day history of vomiting, diarrhea, and altered mental status. Her past medical history was remarkable for AIT and hypokinetic cardiomyopathy. Moreover, she had recently undergone a 2-week course of corticosteroid therapy for vertiginous symptoms, reporting subjective well-being. In ED, she appeared confused and hypotensive. Blood tests revealed a sodium level of 99 mEq/l with normal potassium. Initial treatment with saline infusions were started, followed by ex juvantibus intravenous hydrocortisone awaiting hormone results, which proved consistent with primary adrenal insufficiency (ACTH 1314 pg/ml, cortisol 4.72 ug/dL). Replacement therapy with both hydrocortisone and fludrocortisone was then implemented, with substantial clinical improvement and normalization of sodium levels. However, the patient later developed right heart failure and hypokalemia, which were likely caused by overreplacement and resolved after adjusting the treatment regimen. The final diagnosis of aAD was confirmed by positive adrenal autoantibodies.

Conclusions: aAD should be suspected in each case of severe hyponatremia [2], especially in patients with AIT independent of age. Furthermore, caution is needed in managing high-dose glucocorticoids along with fludrocortisone in elderly patients with cardiac disease to limit the risk of excessive mineralocorticoid activity and heart failure [3].

Aims: This study aimed to confirm the regulatory role and mechanism of circular RNA (circRNA) hsa_circ_0131922 in Papillary Thyroid Carcinoma (PTC) progression.

Background: Accumulating evidence suggests that N6-methyladenosine (m6A)-modified circular RNAs (circRNAs) perform pivotal functions in various malignancies. However, the specific role of the m6A modification of circRNA mediated by METTL3 in Papillary Thyroid Carcinoma (PTC) remains undocumented.

Objective: In this work, we aimed to examine the molecular mechanisms of a novel m6Amodified circRNA, hsa_circ_0131922, in PTC progression.

Methods: Potential circRNA was identified from GEO datasets. The RNA or protein levels of hsa_circ_0131922, METTL3, p53, and p21 were evaluated by qRT-PCR or western blot assays. The various cellular functions were checked by CCK8, wound healing, transwell, and xenograft tumor assays. MeRIP-qPCR was performed to observe the METTL3-mediated m6A modification of hsa_circ_0131922. Furthermore, the interactions between hsa_circ_0131922 and METTL3 in PTC were analyzed by bioinformatics analysis and various rescue experiments.

Results: The levels of hsa_circ_0131922 were markedly downregulated in PTC tissues and cell lines. In addition, the lower hsa_circ_0131922 levels correlated with poor prognosis in PTC patients. The hsa_circ_0131922 overexpression reduced the malignant phenotypes of PTC cells and activated the p53/p21 pathway. Bioinformatic analysis showed the m6A-modified sites of hsa_circ_0131922, and a positive correlation between hsa_circ_0131922 and METTL3. Moreover, overexpression of METTL3 increased the levels of m6A modification of hsa_circ_0131922. Mechanistically, the anti-tumor effects of hsa_circ_0131922 overexpression have been found to be partially reversed by silencing METTL3 in vivo and in vitro.

Conclusion: The results have demonstrated m6A-modified hsa_circ_0131922 by METTL3 to attenuate the progression of PTC by regulating the p53 pathway. Therefore, hsa_circ_0131922 could be a predictive prognostic biomarker and therapeutic target for PTC.

One important phytochemical is naringenin, which belongs to the flavanone class of polyphenols. It is found in citrus fruits, such as grapefruits, but it can also be found in tomatoes, cherries, and other food-grade medicinal plants. Naringenin has a significant chemotherapeutic promise, as several investigations have conclusively shown. Therefore, the goal of this review is to synthesize the literature that has been done on naringenin as a possible anti-cancer agent and clarify the mechanisms of action that have been described in treatment plans for different kinds of cancer. In a variety of cancer cells, naringenin works by affecting several pathways associated with cell cycle arrest, anti-metastasis, apoptosis, anti-angiogenesis, and DNA repair. It has been shown to alter several molecular targets linked to the development of cancer, such as drug transporters, transcription factors, reactive nitrogen species, reactive oxygen species, cellular kinases, and inflammatory cytokines and regulators of the cell cycle. In summary, this research provides significant insights into the potential of naringenin as a strong and prospective candidate for use in medicines, nutraceuticals, functional foods, and dietary supplements to improve the management of carcinoma.

Background: Bone metabolic diseases such as osteoporosis are caused by disruption of the metabolic balance between osteoblasts and osteoclasts. Thousands of papers have been published on osteoporosis and bone metabolizing cells. The purpose of this study is to draw the publication trend of highly cited literature in this field through bibliometrics and to explore the research hotspot analysis.

Objective: This paper provides a comprehensive analysis of the impact of countries/regions, research institutions, authors, keywords, relevant journals, and references in the field of osteoporosis and bone metabolic cells research, with a specific focus on the theme of "Osteoporosis and bone metabolic cells". Furthermore, utilizing bibliometric methods, the study aims to offer valuable insights and references for future research endeavors, as well as clinical prevention and treatment strategies in this domain.

Methods: The Web of Science [WOS] Core Collection database was examined in order to identify articles with high citation counts from 2013 to 31 October 2023. The citation counts, authors, year of publication, source, journal, geographical origin, subject, article type, and level of evidence were further analyzed using the R bibliometric package. The VOSviewer software was utilized to visualize word co-occurrence in a total of 251 articles.

Results: Our search strategy included 251 highly cited articles published between 2013 and 2023 in the field of osteoporosis and bone metabolic cells. The number of publications in this field remains consistently high, indicating ongoing research interest. Notably, the United States has made significant achievements and contributions in this area. Xie Hui, Cao Xu, and Goodman, Stewart are among the main contributors to these advancements. NATURE MEDICINE has the highest journal impact factor of 82.9, highlighting its prominence. The JOURNAL OF BONE AND MINERAL RESEARCH ranks first with 1,322 citations. Keyword research topics in this field include osteoclast differentiation, osteoblast differentiation, and mesenchymal stem cells. Through citation analysis, we found that 195 articles have been cited more than 100 times, demonstrating their significance and impact.

Conclusion: This study analyzed the relationship between osteoporosis and bone metabolic cells using a bibliometric method. The results of these analyses can help researchers gain a more direct and scientific understanding of trends in the field. Additionally, it can provide guidance in identifying hot research directions and offer new ideas for the prevention and treatment of osteoporosis.

Background: Central hypothyroidism and autoimmune hyperthyroidism are contrasting pathologies requiring careful hormone monitoring for restoring euthyroidism. Their coexistence is rare and challenging for clinicians [1, 2].

Case report: We have, herein, presented the case of a 41-year-old female patient with an unremarkable clinical history except for chronic autoimmune thyroiditis in euthyroidism. At the 21st week of gestation, she experienced a spontaneous abortion. The patient underwent an assessment of the uterine cavity, which was complicated by bleeding and hypotensive shock. In the postoperative course, the patient presented worsening headache, and after an MRI, the diagnosis of pituitary apoplexy due to an ischemic-hemorrhagic base was made. Laboratory tests showed anterior panhypopituitarism. Multiaxial replacement therapy was initiated with hydrocortisone, levothyroxine (LT4), and subsequently estrogen-progestin and GH. After two years of good recovery with stable LT4 dosage, the patient experienced palpitations and fine tremors; blood tests showed hyperthyroidism with suppressed Thyroid-stimulating Hormone (TSH) levels and elevated free thyroid fractions and anti-TSH receptor antibodies. Diagnosis of Graves' disease was made, and therapy with methimazole was initiated. During antithyroid therapy, TSH remained persistently suppressed, consistent with the underlying central hypothyroidism. This condition required close follow-up, with monitoring based solely on free thyroid hormone levels. After six months of antithyroid therapy, disease remission was achieved, with negative antibodies and mild hypothyroxinemia. Therefore, methimazole was discontinued and replacement therapy gradually resumed until optimal hormone levels were reached.

Conclusion: This case is unique demonstrating autoimmune hyperthyroidism to coexist with central hypothyroidism, rendering TSH a misleading disease progression indicator. Consequently, managing Graves' disease has become more complex and challenging.

Obesity is now recognised as an emerging public health problem across the globe. Its incidence has been growing in the last two decades. Furthermore, as per the obesity treatment guidelines, a comprehensive approach that incorporates behavioural treatment, medications, lifestyle modifications, and/or bariatric surgery is the best way to manage weight. A novel dual agonist of Glucose-dependent insulinotropic peptide (GIP) and Glucagon-like peptide -1 (GLP- 1) receptors, Tirzepatide, was recently approved for the management of obesity. Tirzepatide manages blood sugar levels and enhances weight loss more than GLP-1 receptor agonists.

Introduction: Chronic diabetic wounds pose a significant threat to the health of diabetic patients, representing severe and enduring complications. Globally, an estimated 2.5% to 15% of the annual health budget is associated with diabetes, with diabetic wounds accounting for a substantial share. Exploring new therapeutic agents and approaches to address delayed and impaired wound healing in diabetes becomes imperative. Traditional Chinese medicine (TCM) has a long history and remarkable efficacy in treating chronic wound healing. In this study, all topically applied proprietary Chinese medicines (pCMs) for wound healing officially approved by the National Medical Products Administration (NMPA) were collected from the NMPA TCM database. Data mining was employed to obtain a high-frequency TCM ingredients pair, Pearl-Borneol (1:1).

Method: This study investigated the effect and molecular mechanism of the Pearl-Borneol pair on the healing of diabetic wounds by animal experiments and metabolomics. The results from animal experiments showed that the Pearl-Borneol pair significantly accelerated diabetic wound healing, exhibiting a more potent effect than the Pearl or Borneol treatment alone. Meanwhile, the metabolomics analysis identified significant differences in metabolic profiles in wounds between the model and normal groups, indicating that diabetic wounds had distinct metabolic characteristics from normal wounds. Moreover, Vaseline-treated wounds exhibited similar metabolic profiles to the wounds from the model group, suggesting that Vaseline might have a negligible impact on diabetic wound metabolism. In addition, wounds treated with Pearl, Borneol, and Pearl-Borneol pair displayed significantly different metabolic profiles from Vaseline-treated wounds, signifying the influence of these treatments on wound metabolism. Subsequent enrichment analysis of the metabolic pathway highlighted the involvement of the arginine metabolic pathway, closely associated with diabetic wounds, in the healing process under Pearl- Borneol pair treatment. Further analysis revealed elevated levels of arginine and citrulline, coupled with reduced nitric oxide (NO) in both the model and Vaseline-treated wounds compared to normal wounds, pointing to impaired arginine utilization in diabetic wounds. Interestingly, treatment with Pearl and Pearl-Borneol pair lowered arginine and citrulline levels while increasing NO content, suggesting that these treatments may promote the catabolism of arginine to generate NO, thereby facilitating faster wound closure. Additionally, borneol alone significantly elevated NO content in wounds, potentially due to its ability to directly reduce nitrates/nitrites to NO. Oxidative stress is a defining characteristic of impaired metabolism in diabetic wounds.

Results: The result showed that both Pearl and Pearl-Borneol pair decreased the oxidative stress biomarker methionine sulfoxi