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The Journal of Investigative Dermatology Jun 2024Systemic sclerosis (SSc) is characterized by intractable multiorgan fibrosis caused by vascular and immune dysfunction. Currently, effective therapeutic options for...
Systemic sclerosis (SSc) is characterized by intractable multiorgan fibrosis caused by vascular and immune dysfunction. Currently, effective therapeutic options for patients with SSc are limited. Nitrate, an abundant nutrient in the diet, has been demonstrated to be preventative and therapeutic for several diseases. To determine whether nitrate can slow or reverse SSc progression, topical application of nitrate delivered by dissolving microneedles was used to treat a bleomycin (BLM)-induced dermal fibrosis mouse model. In this study, nitrate considerably attenuated dermal thickness, stiffness, and collagen deposition. Bulk RNA sequencing of skin revealed that Cd4 was a key hub gene in SSc nitrate therapy. Additionally, BLM-induced cytokines and chemokines were inhibited by nitrate, and CD4 T cells infiltration markedly declined. Il4, Il6, Il13, and Tgfb expression in CD4 T cells isolated from skin biopsies also significantly decreased. Mechanistically, Il1rl1, a type2 immune response inducer, was markedly repressed in isolated CD4 T cells and dermal tissues after nitrate treatment. Remarkably, compared with wild type mice, mice lacking Il1rl1 showed impaired transcriptional profiles after intradermal BLM injection. Adoptive transfer of ST2CD4 T cells promoted bleomycin-induced Rag2 mice dermal fibrosis. Collectively, these findings demonstrate that nitrate targeting ST2CD4 T cells is an effective therapeutic option for SSc.
PubMed: 38945439
DOI: 10.1016/j.jid.2024.06.1273 -
Journal of Oral Biosciences Jun 2024Xerostomia, a common complication of type 2 diabetes, leads to an increased risk of caries, dysphagia, and dysgeusia. Although anti-vascular endothelial growth factor...
OBJECTIVES
Xerostomia, a common complication of type 2 diabetes, leads to an increased risk of caries, dysphagia, and dysgeusia. Although anti-vascular endothelial growth factor (VEGF) antibodies, such as ranibizumab (RBZ), have been used to treat diabetic retinopathy, their effects on the salivary glands are unknown. This study evaluated the effects of RBZ on salivary glands to reduce inflammation and restore salivary function in a mouse model of type 2 diabetes.
METHODS
Male KK-A mice with type 2 diabetes (10-12 weeks old) were used. The diabetes mellitus (DM) group received phosphate-buffered saline, while the DM + RBZ group received an intraperitoneal administration of RBZ (100 μg/kg) 24 h before the experiment.
RESULTS
Ex vivo perfusion experiments showed a substantial increase in salivary secretion from the submandibular gland (SMG) in the DM + RBZ group. In addition, the mRNA expression levels of TNF-α and IL-1β were considerably lower in this group. In contrast, those of aquaporin 5 were substantially higher in the DM + RBZ group, as revealed by quantitative reverse transcription PCR. Furthermore, the number of lymphocyte infiltration spots in the SMG was notably lower in the DM + RBZ group. Finally, intracellular Ca signaling in acinar cells was considerably higher in the DM + RBZ group than that in the DM group.
CONCLUSION
Treating a type 2 diabetic mouse model with RBZ restored salivary secretion through its anti-inflammatory effects.
PubMed: 38944342
DOI: 10.1016/j.job.2024.06.011 -
The American Journal of Dermatopathology Jun 2024Microsecretory adenocarcinoma (MSA) was first described in 2019 as a low-grade salivary gland neoplasm of intraoral origin with distinct histopathologic features and a...
Microsecretory adenocarcinoma (MSA) was first described in 2019 as a low-grade salivary gland neoplasm of intraoral origin with distinct histopathologic features and a characteristic MEF2C::SS18 fusion. Recently, skin was also identified as a primary site for MSA in a report by Bishop et al. Due to its rarity and resemblance to other adnexal tumors, MSA is a challenging diagnosis. Herein, we present a case of cutaneous MSA that was unique for the presence of a significant microcystic component and marked adnexal hyperplasia, which mimicked myxoid microcystic adnexal carcinoma (MAC). A 58-year-old presented with a 1 year history of an enlarging eyelid nodule. Histopathologic analysis revealed dermal tumor composed of small tubules containing inspissated bluish mucinous material. Accompanying marked adnexal hyperplasia and many microcysts were also present. Tumor cells expressed S100 protein, which is distinct from MAC, while p63 immunohistochemistry showed marked loss of myoepithelial labeling, as is common in primary adenocarcinomas. Next generation gene sequencing detected the characteristic MSA fusion protein MEF2c::SS18. We report a novel presentation of MSA that simulated MAC because of the presence of associated microcystic change. The presence of S100 immunopositivity and the identification of MEF2C::SS18 fusion confirmed the diagnosis of cutaneous MSA.
PubMed: 38941552
DOI: 10.1097/DAD.0000000000002788 -
Head and Neck Pathology Jun 2024Myoepithelioma is a benign salivary gland tumor. Central myoepitheliomas are very rare. The aim of this report was to describe a case of maxillary myoepithelioma. A...
Myoepithelioma is a benign salivary gland tumor. Central myoepitheliomas are very rare. The aim of this report was to describe a case of maxillary myoepithelioma. A 14-year-old female patient presented with an multilocular lesion in the anterior maxilla, with nearly 8 months of duration. The lesion was asymptomatic, and the patient's dental history was unremarkable. The diagnostic hypothesis was an odontogenic tumor. Biopsy specimen consisted of nests of plasmacytoid cells in a myxoid stroma without duct formation. No cellular atypia or bone and cartilage formation were noted. The neoplastic cells were positive for Pan-cytokeratin, S100, CK7, and CK8. The final diagnosis was myoepithelioma. The patient was treated by surgical excision followed by bone curettage, and no signs of recurrence were found after 8 years of treatment.
Topics: Humans; Female; Myoepithelioma; Adolescent; Maxillary Neoplasms; Biomarkers, Tumor
PubMed: 38940938
DOI: 10.1007/s12105-024-01665-y -
Clinical Cancer Research : An Official... Jun 2024To assess efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive, unresectable or recurrent/metastatic salivary gland carcinoma (URM-SGC).
PURPOSE
To assess efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive, unresectable or recurrent/metastatic salivary gland carcinoma (URM-SGC).
PATIENTS AND METHODS
This was an open-label, single-arm, multicenter phase II study for patients with AR-positive URM-SGC. The primary endpoint was the overall response rate (ORR) by an independent central radiology review (ICRR) in the first 24 response evaluable patients who had been observed at least 24 weeks from study initiation (primary RE patients). The efficacy was to be declared when at least 8 of the 24 primary RE patients responded.
RESULTS
31 patients were enrolled. In the first 24 primary RE patients with a median follow-up of 7.4 months, confirmed ORR by ICRR was 25.0% (6/24 patients; 95%CI: 9.8%-46.7%; P =0.11 (one-sided)), which did not meet the predefined criteria of efficacy. Clinical benefit rate (ORR + rate of stable disease for at least 24 weeks) and median progression-free survival were 50.0% and 7.4 months, respectively. Both median duration of response and overall survival were not reached. Exploratory analyses showed a better ORR of 54.5% (6/11) in patients with AR-positivity ≥ 70% and no history of prior systemic therapy. Grade 3 or higher treatment-emergent adverse events were reported in 35.5% (11/31), which included skin rash, anemia, leukopenia, and cancer pain.
CONCLUSIONS
Although this study did not meet the predefined efficacy criteria, apalutamide plus goserelin showed clinically meaningful efficacy in a subset of patients with AR-positive SGC and safety consistent with prior experience in prostate cancer.
PubMed: 38940667
DOI: 10.1158/1078-0432.CCR-24-0455 -
Medeniyet Medical Journal Jun 2024Tumors occurring in the submandibular space are infrequent among pediatric patients, and benign peripheral nerve tumors in this region are exceptionally rare. This study...
Tumors occurring in the submandibular space are infrequent among pediatric patients, and benign peripheral nerve tumors in this region are exceptionally rare. This study describes the uncommon occurrence of a schwannoma in the submandibular space in a child and describes its management. A 7-year-old child presented with a gradually enlarging swelling over a 7-month period in the submandibular region, clinically resembling a salivary gland tumor. There were no associated marginal mandibular, lingual, or hypoglossal nerve palsy. The mass was excised completely, and histopathological examination revealed it to be a schwannoma. It is appropriate to consider benign peripheral nerve tumors, such as schwannoma, in the differential diagnosis of submandibular space tumors in children.
PubMed: 38940503
DOI: 10.4274/MMJ.galenos.2024.37729 -
Frontiers in Bioscience (Landmark... Jun 2024Hormone receptors exert their function through binding with their ligands, which results in cellular signaling activation mediated by genomic or non-genomic mechanisms....
BACKGROUND
Hormone receptors exert their function through binding with their ligands, which results in cellular signaling activation mediated by genomic or non-genomic mechanisms. The intrinsic molecular communication of tick and its host comprises an endocrine regulation involving hormones. In the present study, we performed a molecular and analysis of a Membrane Associated Progesterone Receptor in (RmMAPRC).
METHODS
The RmMAPRC protein sequence was analyzed with bioinformatics tools, and its structure was characterized by three-dimensional (3D) modeling and molecular docking. A semi-quantitative reverse transcription and polymerase chain reaction (sqRT-PCR) assessed the gene presence and relative expression in tick organs and embryonic cells.
RESULTS
relative expression in salivary glands, ovaries, and embryonic cells showed overexpression of 3%, 13%, and 24%, respectively. Bioinformatic analysis revealed that RmMAPRC corresponded to a Progesterone Receptor Membrane Component 1 (RmPGRMC1) of ~23.7 kDa, with an N-terminal transmembrane domain and a C-terminal Cytochrome b5-like heme/steroid binding domain. The docking results suggest that RmPGRMC1 could bind to progesterone (P4), some progestins, and P4 antagonists. The phylogenetic reconstruction showed that spp. MAPRC receptors were clustered in a clade that includes , , and (RmMAPRC), and mammals and helminths MAPRC receptors clustered in two separated clades away from ticks.
CONCLUSIONS
The presence of RmPGRMC1 highlights the importance of transregulation as a conserved adaptive mechanism that has succeeded for arthropod parasites, making it a target for tick control.
Topics: Animals; Rhipicephalus; Receptors, Progesterone; Progesterone; Cattle; Molecular Docking Simulation; Host-Parasite Interactions; Female; Amino Acid Sequence; Protein Binding; Phylogeny
PubMed: 38940045
DOI: 10.31083/j.fbl2906238 -
Case Reports in Otolaryngology 2024Absence or aplasia of the major salivary glands is an uncommon diagnosis and is often associated with other congenital abnormalities. Agenesis of a single submandibular...
BACKGROUND
Absence or aplasia of the major salivary glands is an uncommon diagnosis and is often associated with other congenital abnormalities. Agenesis of a single submandibular gland, however, is an even more rare phenomenon and can be associated with hypertrophy of other salivary glands.
METHODS
A 48-year-old female presented to the clinic with a left-sided neck mass below her mandible. Workup including a CT scan showed an absent left-sided submandibular gland and an enlarged sublingual gland protruding through the mylohyoid muscle.
RESULTS
The patient underwent a transoral resection of the mass with subsequent resolution of the mass. The pathology returned as normal salivary gland tissue.
CONCLUSIONS
Sublingual gland hypertrophy is a very uncommon presentation for a patient with a neck mass. This situation can arise in the setting of submandibular gland aplasia and compensatory hypertrophy of other salivary glands.
PubMed: 38939733
DOI: 10.1155/2024/8610465 -
Frontiers in Cellular and Infection... 2024The Asian citrus psyllid (ACP) Kuwayama is the leading vector of Liberibacter asiaticus (Las), the causative agent of citrus Huanglongbing (HLB) disease. The...
The Asian citrus psyllid (ACP) Kuwayama is the leading vector of Liberibacter asiaticus (Las), the causative agent of citrus Huanglongbing (HLB) disease. The distribution and dynamics of Las within ACP are critical to understanding how the transmission, spread and infection of Las occurs within its host vector in nature. In this study, the distribution and titer changes of Las in various tissues of ACP 5 instar nymphs and adults were examined by (FISH) and real-time quantitative PCR (qPCR) techniques. Results demonstrated that 100% of ACP 5 instar nymphs and adults were infected with Las following feeding on infected plants, and that Las had widespread distribution in most of the tissues of ACP. The titers of Las within the midgut, salivary glands and hemolymph tissues were the highest in both 5 instar nymphs and adults. When compared with adults, the titers of Las in these three tissues of 5 instar nymphs were significantly higher, while in the mycetome, ovary and testes they were significantly lower than those of adults. FISH visualization further confirmed these findings. Dynamic analysis of Las demonstrated that it was present across all the developmental ages of ACP adults. There was a discernible upward trend in the presence of Las with advancing age in most tissues of ACP adults, including the midgut, hemolymph, salivary glands, foot, head, cuticula and muscle. Our findings have significant implications for the comprehensive understanding of the transmission, dissemination and infestation of Las, which is of much importance for developing novel strategies to halt the spread of Las, and therefore contribute to the efficient prevention and control of HLB.
Topics: Animals; Hemiptera; Insect Vectors; Plant Diseases; Nymph; Citrus; In Situ Hybridization, Fluorescence; Rhizobiaceae; Real-Time Polymerase Chain Reaction; Salivary Glands; Hemolymph
PubMed: 38938879
DOI: 10.3389/fcimb.2024.1408362 -
Frontiers in Immunology 2024Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently...
Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody-positive patients. Twelve to 30% and 50 to 62% of these antibodies were disease-specific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases.
Topics: Humans; Salivary Glands; Autoantibodies; Myositis; Female; Male; Lung; Middle Aged; Bronchoalveolar Lavage Fluid; Adult; B-Lymphocytes; Lung Diseases, Interstitial; Autoantigens; Antibodies, Antinuclear; Aged
PubMed: 38938569
DOI: 10.3389/fimmu.2024.1265792