Introduction: Multiple autoimmune syndrome (MAS) type 3 is characterized by the coexistence of autoimmune thyroid disease with other organ-specific or systemic autoimmune disorders, excluding adrenal insufficiency. MAS represents a form of polyautoimmunity, in which shared immunological mechanisms contribute to clustering of multiple autoimmune diseases within a single individual. Recent studies suggest the clinical spectrum of MAS continues to expand, with increasing recognition of diverse autoimmune combinations across different organ systems. However, detailed clinical characterization of MAS type 3 involving overlapping endocrine and neuromuscular autoimmune diseases in young adults remains limited. Cases: We report four young adults (aged 21–37 years) with heterogeneous manifestations of MAS type 3 involving endocrine and systemic autoimmune diseases. Autoimmune thyroid disease was identified in three patients, all diagnosed with Graves’ disease with suppressed thyroidstimulating hormone, elevated free thyroxine, and positive thyrotropin receptor antibodies. Autoimmune diabetes was present in three patients, including latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus, with variable glycemic control (hemoglobin A1c range 6.7–13.9%) and C-peptide levels ranging from preserved to markedly reduced. Myasthenia gravis was observed in three patients. Additional autoimmune conditions included systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and ulcerative colitis. Notably, rare combinations such as Graves’ disease with LADA and myasthenia gravis, as well as coexistence with systemic autoimmune diseases, were identified. All patients received individualized multidisciplinary management. Clinical and biochemical improvement was observed in all cases, with stabilization of both endocrine and systemic autoimmune manifestations. Conclusion This case series highlights the heterogeneous and expanding clinical spectrum of MAS type 3, including rare combinations of autoimmune endocrine and systemic diseases in young adults. Early recognition of autoimmune clustering and comprehensive screening are essential to optimize management and improve outcomes. These findings provide insights into autoimmune disease clustering and support the need for proactive multidisciplinary management strategies.
Young Adult ; Humans ; Autoimmune Diseases

Introduction: Thalassemia is a hemoglobin synthesis disorder associated with chronic anemia and transfusion-related iron overload, which predisposes patients to multiple endocrine complications. Iron deposition in the pituitary and gonads may result in growth hormone deficiency (GHD) and hypogonadism. Empty sella syndrome (ESS), characterized by herniation of the subarachnoid space into the sella turcica, may also contribute to hypopituitarism. The coexistence of thalassemia-related endocrinopathies, ESS, and autoimmune thyroid disease is rare and presents significant diagnostic complexity. Case: A 27-year-old female with transfusion-dependent thalassemia on deferiprone presented with secondary amenorrhea and short stature. Her height was 145 cm (below the target range of 140.5–157.5 cm), body mass index 17.3 kg/m², and Tanner stage M3P1. Laboratory evaluation revealed elevated thyroidstimulating hormone (10.92 mIU/L) with low-normal free thyroxine 4 (11.4 pmol/L), consistent with primary hypothyroidism. Thyroid ultrasound demonstrated features of chronic thyroiditis, and anti-thyroid peroxidase antibodies (8.18 IU/mL) supported a diagnosis of Hashimoto’s thyroiditis. Insulin-like growth factor-1 was markedly reduced (68 ng/mL), indicating GHD. Morning cortisol was within normal range (14.5 µg/dL). Gonadotropins were inappropriately low-normal (folliclestimulating hormone 7.42 mIU/mL, luteinizing hormone 11.41 mIU/mL) with low estradiol (26.49 pg/mL), suggesting hypogonadotropic hypogonadism. Skeletal survey showed thalassemia-related bone changes, including trabecular coarsening and metaphyseal widening, with a predicted adult height of 142.7 cm. Pituitary magnetic resonance imaging revealed an empty sella. Conclusion Thalassemia must be recognized not only as a primary hematologic condition but also as a complex multisystem disorder with profound endocrine implications. Furthermore, the co-occurrence of these conditions with rare manifestations such as ESS and Hashimoto’s thyroiditis underscores the diagnostic complexity faced by clinicians. Therefore, early detection and rigorous, regular endocrine screening are essential to optimize management strategies and improve the long-term quality of life for patients with thalassemia.
Empty Sella Syndrome ; Growth Hormone ; Thalassemia ; Thyroiditis

Introduction: Nonfunctioning pituitary adenomas (NFPA) may cause central hypothyroidism due to pituitary compression, often presenting with low thyroid-stimulating hormone (TSH). However, suppressed TSH in this setting should not automatically be attributed to pituitary dysfunction, as primary hyperthyroidism—such as Graves’ disease—may rarely coexist. Distinguishing between these disorders is essential to avoid misdiagnosis and inappropriate management. Case: A 42-year-old female presented with intermittent headache, visual field impairment, palpitations, fine tremors, and weight loss. Physical examination revealed visual field deficits and no goiter. Laboratory evaluation showed cortisol level of 1 µg/dL (normal: 3.7–19.4 µg/dL), luteinizing hormone 1.62 mU/L (normal: 2.4–12.6 mU/L), follicle-stimulating hormone 5.01 mU/L (normal: 3.5–12.5 mU/L), free thyroxine 4 28.32 pmol/L (normal: 12–22 pmol/L), TSH 0.02 µIU/mL (normal: 0.27–4.2 µIU/mL), and prolactin 70.84 ng/mL. Thyrotropin receptor antibody (TRAb) was 3.53 IU/L, confirming Graves’ disease. Contrast-enhanced brain magnetic resonance imaging demonstrated a pituitary macroadenoma (2.13 × 2.28 × 3.05 cm) with optic chiasm compression. The patient was diagnosed with NFPA, Graves’ disease, secondary adrenal insufficiency, possible hypogonadotropic hypogonadism, and hyperprolactinemia likely due to the stalk effect. Preoperative management included hydrocortisone replacement and antithyroid therapy. The patient subsequently underwent transsphenoidal surgery with appropriate perioperative care. Postoperatively, no new pituitary hormone deficiencies were observed. She was maintained on thiamazole 10 mg daily with clinical improvement and remains under regular follow-up. Conclusion This case highlights a rare but clinically important coexistence of NFPA and Graves’ disease. Suppressed TSH in patients with pituitary adenoma should not be assumed to reflect pituitary dysfunction without thorough evaluation. Comprehensive thyroid assessment is crucial to ensure accurate diagnosis and appropriate management.
Pituitary Neoplasms ; Graves Disease

Aims: This study was designed to investigate the antibacterial properties of the sericin protein Bombyx mori and Samia cynthia ricini against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus strains. Methodology and results: Sericin protein was extracted from the cocoons of B. mori races A, B, C, D, F1-1, F1-2 and S. ricini from Indonesia using a degumming process. The extracted sericin protein was evaluated as anti-microbials using Kirby Breuer disc diffusion, spectrometer measurement in decreasing OD value and imaging scanning electron microscope (SEM). The tests revealed that sericin protein from B. mori was more capable of inhibiting bacteria S. aureus than E. coli. Sericin protein from S. ricini was also capable of strongly inhibiting both S. aureus and E. coli bacteria. The sericin proteins of B. mori and S. ricini were found to reduce the number of S. aureus and E. coli bacteria as the OD value decreased at a concentration of 9%. The SEM imaging suggests that sericin B. mori and S. ricini proteins caused changes in cell morphology in S. aureus and E. coli bacteria, resulting in bacterial cell function disruption and death. Conclusion, significance and impact of study Bombyx mori and S. ricini sericin proteins were found to act against S. aureus and E. coli bacteria. Therefore, sericin protein has a greater antibacterial activity against Gram-positive strain S. aureus.
Anti-Bacterial Agents ; Sericins ; Bombyx ; Lepidoptera ; Escherichia coli ; Staphylococcus aureus

ABSTRACT The goal of endodontic treatment is to prevent and control of pulp and periradicular infections. Calcium hydroxide has a beneficial biological property as an intracanal medicament and can be combined with cresotin to disinfect bacteria in root canals, especially Enterococcus faecalis (E. faecalis) which is the most frequently isolated strain in the root canals. The aim of this study was to investigate in vitro the antimicrobial activity of calcium hydroxide, cresotin, and combination calcium hydroxide and cresotin (Ca[OH]2+Cresotin, 1:1 and 1:2) against E. faecalis. Antibacterial activity was determined by the agar diffusion method. The test medicaments were placed inside the hole that made in the inoculated agar medium. The zone of growth inhibition was measured and recorded after incubation for each plate, and the result was analysed statistically with ANOVA. The in vitro antimicrobial effects of combination calcium hydroxide and cresotin (Ca[OH]2+Cresotin, 1:2) has more prominent antimicrobial activity than others, and calcium hydroxide is more effective than cresotin alone. The antimicrobial activity of combined calcium hydroxide and cresotin is more effective in killing E. faecalis in comparison to the other treatments.
Calcium Hydroxide--therapeutic use ; Root Canal Therapy ; Enterococcus faecalis

Introduction: Anadara-granosa synthesization through hydrothermal-method produces beta-tricalcium(beta-TCP), a biomaterial that is able to provide a pathway for calcium-ions in dentin reparative formation thus qualifies TCP as pulp-capping material.Nanoencapsulation is needed as calcium-ions have shown its rapid solubility which is the main cause of high probability risk of tunnel defect.The present study aimed to understand the correlation between stirring time, particle size and level of calcium of beta-TCP nanoencapsulation synthesized from Anadara-granosa-shells. Methods: Anadara-granosa-shells powder was hydrothermically-processed for 18hours and sintered for 3hours. After homogenous beta-TCP powder mixed with aquadest in magnetic stirrer acquired, Na-alginate was added during the stirring process following CaCl2 drop by drop into the mixture.Sample divided into 6-test groups according to the stirring time; P1-one hours;P2-two hours;P3-three hours;P4-four hours;P5-five hours;P6-six hours.All samples centrifuged at 2500rpm for 6minutes and freeze-dried for 12hours.PSA-test and Calcium level-test were performed on the sample test groups, followed by ANOVA-test and post hoc with significance level of P-value=0,05. Results: Data showed average of particle-sizes P1=±336.44; P2=±325.7; P3=±340.94; P4=±452.6; P5=±556.6; P6=± 593.93.ANOVA-test result indicated a significant difference and backed up by Gomes howell test result.Significant differences were found between group first-second-third and group four-five-six also between group five and group six. Calcium level test result was P1=±10.41; P2=±9.53; P3=±9.87; P4=±5.52; P5=±5.33; P6=±5.25.ANOVA-test showed a significant difference and supported by post-hoc LSD-test.Significant differences noted between group one and other groups also between group-two-three and group-four-five-six. Conclusion: In the process of Nanoencapsulation of Anadara-granosa-shells, particle size gradually increased and calcium level gradually decreased along with the longer stirring time was performed.

Previous study on the gene expression profile of human MDS by using microarray discovered that transcription of RAP1GAP was up-regulated, which was confirmed by quantitative RT-PCR in expanding cohort of MDS patients. This study was pourposed to investigate the expression of RAP1GAP in human MDS and its clinical relevance. The expression of RAP1GAP in bone marrow cells of 19 MDS patients was detected by flow cytometry and was compared with that in patients with non-malignant blood diseases and acute leukemias, meanwhile the relevance between expression level of RAP1GAP and hemoglobin, leukocytes, platelets, blasts percentage in bone marrow cells and IPSS score was analyzed. The results indicated that the expression level of RAP1GAp in MDS patients significantly increased as compared with patients with non-malignant blood diseases or AML (8.42 +/- 8.37% vs 2.97 +/- 4.75% or 2.26 +/- 4.24%). Among MDS patients, the expression level of RAP1GAP in MDS-RA was significantly higher than that in MDS-RAEB (11.64 +/- 9.07% vs 4.37 +/- 4.65%). However, no definitive correlation of expression level with above-mentioned clinical parameters was found in detected patients with DMS. In conclusion, the expression of RAP1GAP in MDS patients obviously increases, the relationship between expression level of RAP1GAP and laboratory hematological parameter and IPSS score does not be confirmed. The role played by RAP1GAP expression in the pathogenesis of MDS and its clinical significance during progression of MDS towards AML deserves further studies.
Adult ; Aged ; Aged, 80 and over ; Female ; Flow Cytometry ; GTPase-Activating Proteins ; genetics ; metabolism ; Gene Expression Profiling ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; metabolism

Rap1 is a small G protein belonging to the RAS superfamily. Rap1 signalling has effects on cell growth, cell proliferation and involves in regulation of the mitogen activated protein (MAP) kinase or ERK (extracellular signal regulated kinase) cascade. Rap1 will directly activate ERK through B-Raf. B-Raf is a member of Raf family, and presents in neuronal and hematopoietic cells. Oncogenic mutations of gene RAS are most frequent and detected in 20% - 30% of human leukemias and 10% - 15% of MDS cases. The review summarizes the regulatory function of Rap1 in development of hematopoietic cells and effect of Rap1 in hematologic malignancies.
Hematologic Neoplasms ; genetics ; metabolism ; Humans ; Signal Transduction ; rap1 GTP-Binding Proteins ; genetics ; metabolism