Gland Damage Research Articles

Prolonged exposure to NaAsO2 induces thyroid dysfunction and inflammatory injury in Sprague‒Dawley rats, involvement of NLRP3 inflammasome‒mediated pyroptosis.

Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in Sprague‒Dawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial-mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions.

Melatonin Mitigates Cisplatin-Induced Submandibular Gland Damage by Inhibiting Oxidative Stress, Inflammation, Apoptosis, and Fibrosis.

The study aims to examine the possible effect of melatonin against cisplatin-induced submandibular degeneration in experimental rats exploring its ameliorative mechanisms. Rats were classified into four experimental groups; control group; melatonin group; cisplatin group; and cisplatin+melatonin group. Submandibular tissues were collected. Biochemical, histopathological, and immunohistopathological examination and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis were performed. The results indicate that intraperitoneal administration of melatonin (30 mg/kg body weight) alongsidecisplatin significantly elevated submandibular glands (SMG) and reduced glutathione (GSH) and superoxide dismutase (SOD) levels (p < 0.001), while it reducedmalondialdehyde (MDA) levels, NF-κB gene expression, the protein level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), immunoexpression of low-dose cyclooxygenase-2 (Cox-2), and CD68. Moreover, melatonin reduced immune and gene expression of alpha-smooth muscle actin (α-SMA), immunoexpression of caspase-3, and gene expression of Bax in comparison to the cisplatin group. Melatonin attenuated cisplatin-induced submandibular destruction alleviating SMG oxidative stress, inflammation, and fibrosis in addition to halting cellular apoptosis, sheds light on its usage in clinical application.

Mitochondria-targeted NIR molecular probe for detecting viscosity of gland damage and SO2 in actual samples

Glandular damage can be caused by various factors, including disease, trauma, or other abnormalities within the organism. The viscosity of the gland is one of the important indicators to measure the degree of damage. Sulfur dioxide (SO2) is widely used as an important food additive due to its preservative and bleaching properties, but its overuse has serious negative impacts on the environment, so it is urgent to develop a simple detection method. Herein, we designed and synthesized a mitochondria-targeted near-infrared (NIR) fluorescence probe (BDC) for the detection of viscosity and SO2. BDC consisted of a donor-π-acceptor (D-π-A) structure and extended double bonds bridging rotor, which enabled sensitive response to viscosity and intense fluorescence emission. The TICT (twisted intramolecular charge transfer) of BDC was inhibited with an increase in viscosity, accompanied by a significant enhancement of red fluorescence signal with emission wavelength beyond 800 nm. Notably, BDC was able to noninvasively and sensitively monitor the viscosity changes in the glands of non-obese diabetic (NOD) mice model. BDC was utilized for monitoring SO2 in food and environmental samples through Michael addition reactions, providing a straightforward tool for SO2 detection in food safety and environmental monitoring.

Tongue squamous cell carcinoma treated by 5-aminolevulinic acid administrated through Microdrop method

BackgroundPostoperative recurrence of tongue squamous cell carcinoma (TSCC) has always been a clinical problem for patients and doctors. Surgery and radiotherapy are the main treatment methods for TSCC, but reoperation often leads to functional impairment. Side effects of radiotherapy include mucosal gland damage, dry mouth, weakened or lost taste. Improved treatment is needed. ObjectiveTo evaluate the clinical outcome of a patient with TSCC treated with Microdrop aminolevulinic acid (ALA) photodynamic treatment (PDT) twice. MethodsALA was dissolved in 5 % lidocaine and the concentration of ALA was 20 % by Microdrop method. Then, the tumor tissue was expanded 1 cm outward, and the injection points were evenly distributed with an upper and lower left and right interval of 2–3 mm. The 1 ml syringe was used to perform the injection in the skin of the tumor area, and there was a small cuticle at each injection point. A pathologically confirmed patient with TSCC received twice Microdrop ALA-PDT treatments, which were evaluated at 1 month and 4 months later. ResultsAfter 3 h of Microdrop ALA injection, the wavelength of semiconductor laser was set to 630 nm, and the energy of 300 mW /cm2 was irradiated for 30 min. After two treatments, the lesions were not visible, and no recurrence occurred after 4 months of follow-up. The patient's tongue function was well preserved and the cosmetic effect was good. ConclusionMicrodrop ALA-PDT may be effective in the salvage treatment of select tongue squamous cell carcinoma.

Role of Micronutrient Supplementation in the Management of Hashimoto's Thyroiditis: A Review of Current Evidence and Potential Mechanisms of Action

Introduction and objective: Hashimoto's thyroiditis (HT), the most prevalent autoimmune disorder and a primary cause of hypothyroidism globally, leads to thyroid gland damage through lymphocyte infiltration. Pharmacological treatment of HT involves the use of levothyroxine, which in most cases must be taken for life. However, supplementation with micronutrients is often overlooked. Several studies have examined the impact of substances such as selenium, zinc, vitamin B12, and vitamin D on the course of Hashimoto's disease. Review methods: Review and summary of research studies available in open-source format on Google Scholar, PubMed. Abbreviated description of the state of knowledge: Supplementation with selenium, zinc, vitamin D, and B12 shows potential benefits for patients with Hashimoto's disease. Summary: Regular monitoring and tailored supplementation of selenium, zinc, vitamin D, and vitamin B12 can enhance overall health and disease management. Therefore, it is worth considering the supplementation of these micronutrients in the daily routine of patients with Hashimoto's thyroiditis. However, it should be noted that these supplements do not constitute a treatment for Hashimoto's disease and their effect cannot replace the intake of levothyroxine.

Dexmedetomidine on the interplay of IL-6 and STAT3 pathways in adrenal gland damage-induced scalding burns in rats.

Scalding burns are a common form of thermal injury that often leads to systemic complications. Pro-inflammatory cytokines like interleukin-6 (IL-6) and the activation of signal transducer and activator of transcription 3 (STAT3) pathways have been linked to the pathophysiology of organ damage caused by burns. This study aimed to investigate the potential therapeutic effects of dexmedetomidine, an α2-adrenergic receptor agonist with anti-inflammatory properties, on the interplay of IL-6 and STAT3 pathways in adrenal gland damage following scalding burns in rats. Twenty-eight rats were divided randomly into four groups. Rats in group 1 (n=7, control) were given only 0.9% intraperitoneal (i.p.) NaCl. Rats in group 2 (n=7, DEX) were exposed to 25°C water for 17 s on day 1 and received 100 mcg/kg/day dexmedetomidine i.p. for 3 days; for rats in group 3 (n=7, Burn), boiling water of 94°C was applied inside for 17 s. Rats in group 4 (n=7, Burn+DEX) were exposed to 94°C water for 17 s and received 100 mcg/kg/day dexmedetomidine i.p. for 3 days. Adrenal gland tissues were histopathological examined, and STAT3, IL-6, and TUNEL staining were performed using immunohistochemically. Our results revealed that scalding burns increased IL-6 and STAT3 expression in the adrenal glands of rats. Histological analysis demonstrated that dexmedetomidine administration ameliorated adrenal gland damage and reduced inflammatory cell infiltration. Our findings suggest that dexmedetomidine protects the adrenal glands in scalding burns. This protection appears to be mediated, at least in part, by its modulation of IL-6 and STAT3 pathways.

Diagnosis of hypoprolactinemia.

Prolactin is a polypeptide hormone composed of 199 amino acids, synthesized by lactotroph cells. Its primary effects are on the mammary gland and gonadal axes, but it also influences different organs and systems, particularly metabolic functions. Current literature has mainly focused on the diagnosis, monitoring, and treatment of hyperprolactinemia. Due to the lack of a well-established effective treatment for hypoprolactinemia, it is not clinically emphasized. Therefore, data on its diagnosis is limited. Hypoprolactinemia has been associated with metabolic dysfunctions such as type 2 diabetes mellitus, fatty liver, dyslipidemia, fertility problems, sexual dysfunction, and increased cardiovascular disease. While often seen as a part of combined hormone deficiencies due to pituitary damage, isolated prolactin deficiency is rare. Hypoprolactinemia can serve as a marker for extensive pituitary gland damage and dysfunction.Low or undetectable serum prolactin levels and the absence of a sufficient prolactin peak in the thyrotropin-releasing hormone (TRH) stimulation test are considered diagnostic for hypoprolactinemia. Gender appears to influence both basal prolactin levels and TRH stimulation test responses. Basal prolactin levels of, at least, 5 ng/mL for males and 7 ng/mL for females can be used as cut-off levels for normal prolactin reserve. Minimum peak prolactin responses of 18 ng/mL for males and 41 ng/mL for females to TRH stimulation can exclude hypoprolactinemia. However, larger population studies across different age groups and sexes are needed to better define normal basal prolactin levels and prolactin responses to the TRH stimulation test.

Advances in cellular and molecular pathways of salivary gland damage in Sjögren's syndrome.

Sjögren's Syndrome (SS) is an autoimmune disorder characterized by dysfunction of exocrine glands. Primarily affected are the salivary glands, which exhibit the most frequent pathological changes. The pathogenesis involves susceptibility genes, non-genetic factors such as infections, immune cells-including T and B cells, macrophage, dendritic cells, and salivary gland epithelial cells. Inflammatory mediators such as autoantibodies, cytokines, and chemokines also play a critical role. Key signaling pathways activated include IFN, TLR, BAFF/BAFF-R, PI3K/Akt/mTOR, among others. Comprehensive understanding of these mechanisms is crucial for developing targeted therapeutic interventions. Thus, this study explores the cellular and molecular mechanisms underlying SS-related salivary gland damage, aiming to propose novel targeted therapeutic approaches.

MiR-34a promotes mitochondrial pathway of apoptosis in human salivary gland epithelial cells by activating NF-κB signaling

To investigate the potential molecular mechanism of miR-34a in Sjögren's syndrome (SS). Transmission electron microscopy was used to observe the salivary gland tissues of mild and severe SS patients. SS mouse model was constructed and injected with miR-34a antagonist. HSGE cells were transfected with miR-34a mimic. Starbase predicted miR-34a binding sites and validated them with dual-luciferase reporter assays. Immunohistochemistry, HE staining, CCK-8, TUNEL assay, flow cytometry, immunofluorescence and Western Blot were used to investigate the effects of miR-34a on NF-κB signaling and mitochondrial pathway of apoptosis in HSGE cells. Severe SS patients showed obvious mitochondrial damage and apoptosis in salivary glands. MiR-34a was overexpressed and NF-κB signaling is activated in salivary glands of severe SS patients. Inhibition of miR-34a alleviated salivary gland injury in SS mice, as well as inhibited the activation of NF-κB signaling and mitochondrial pathway of apoptosis. In conclusion, miR-34a promoted NF-κB signaling by targeting IκBα, thereby causing mitochondrial pathway apoptosis and aggravating SS-induced salivary gland damage.

The effect of airborne particulate matter 2.5 (PM2.5) on meibomian gland

Exposure to particulate matters in air pollution of 2.5 μm or less (PM2.5) was associated with loss of meibomian glands. The aim of this study was to verify that PM2.5 could directly impact meibomian gland epithelial cells and damage their function. To investigate the impact of PM2.5 on meibomian gland, immortalized human meibomian gland epithelial cells were treated with various concentrations of PM2.5in vitro. Meibomian gland cell microstructure, cell viability, expression of proliferating cell nuclear antigen and IL-1β, and intracellular accumulation of acidic vesicles were measured by transmission electron microscopy, cell counting, Western blot and LysoTracker staining, respectively. To further study the effect of PM2.5in vivo, male C57BL/6J mice were treated with 5 mg/ml PM2.5 or vehicle for 3 months. Corneal fluorescein staining and ocular examinations were done before and after the treatment. Eyelids tissues were processed for morphological studies, immunostaining and Oil Red O staining. Our data suggest that exposure to PM2.5 caused significant meibomian gland dropout, clogged gland orifice and increased corneal fluorescein staining that were consistent with the clinical presentations of meibomian gland dysfunction. Prominent changes in the morphology and ultrastructure of meibomian glands was observed with PM2.5 treatment. PM2.5 promoted ductal keratinization, inhibited cell proliferation, induced cell apoptosis and increased Interleukin-1β production in meibomian gland epithelial cells. This study may explain the association between PM2.5 exposure and meibomian gland dropout observed in clinic. PM2.5 resuspension instillation could be used to induce a meibomian gland dysfunction animal model.

Iguratimod Alleviates Experimental Sjögren's Syndrome by Inhibiting NLRP3 Inflammasome Activation.

Iguratimod (T-614) is a compound widely used as anti-rheumatic drug. This study investigated the effect and underlying mechanism of T-614 on experimental Sjögren's syndrome (ESS). ESS mice model was established by injection of submandibular gland protein. Mice were randomly divided into control, experimental Sjögren's syndrome (ESS), ESS + T-614 (10 mg/kg), ESS + T-614 (20 mg/kg), and ESS + T-614 (30 mg/kg) groups. Human submandibular gland (HSG) were cultured with 0, 0.5, 5, or 50 μg/ml T-614 in the absence or presence of interferon-α (IFN-α). Haematoxylin and eosin (H&E) and cytokine levels were used to detect immune cells activation in submandibular glands. Apoptosis in submandibular glands tissues and cells was determined by TUNEL and flow cytometry. Apoptosis and NLRP3 inflammasome-related proteins were detected by western blotting. T-614 treatment attenuated submandibular gland damage in ESS mice. T-614 administration inhibited submandibular gland cell apoptosis in ESS mice. Furthermore, T-614 blocked inflammatory factor levels and NLRP3 inflammasome activation in the submandibular glands. In vitro, results corroborated that T-614 could protect HSG cells from IFN-α-induced cell apoptosis and inflammation by inhibiting NLRP3 inflammasome activation. Our results expounded that T-614 alleviated ESS by inhibiting NLRP3 inflammasome activation.

Developing a model for aqueous deficient dry eye secondary to periglandular cicatrizing conjunctivitis

PurposeThe current study used various techniques to develop a rabbit animal model of lacrimal gland damage caused by scarring conjunctivitis in the periglandular area. MethodsLeft eyes of New Zealand white rabbits were injected with 0.1 ml of 1M NaOH subconjunctivally around superior and inferior lacrimal gland orifices (Group 1, n = 4), touched with 1M NaOH for 100 s to the superior and inferior fornices with conjunctival denuding (Group 2; n = 4), and electrocauterization to the ductal opening area (Group 3; n = 4). The ocular surface staining, Schirmer I, lacrimal gland, and conjunctival changes were observed at baseline,1, 4, 8, and 12 weeks. The degree of glandular inflammation, conjunctival fibrosis (Masson Trichrome), and goblet cell density (PAS) were also assessed. ResultsAt 12 weeks, the lacrimal glands of group 1 rabbits with periglandular injection showed severe inflammation with mean four foci/10HPF and a significant mean reduction in the Schirmer values by 7.6 mm (P = 0.007). Lacrimal glands had diffuse acinar atrophy, loss of myoepithelial cells, and ductular dilatation. The overlying conjunctiva showed fibrosis, goblet cell loss, and corneal vascularization in the inferotemporal quadrant. No lacrimal gland or ocular surface changes were observed in groups 2 and 3 at 12 weeks, except for localized subconjunctival fibrosis. ConclusionPeriglandular injection of 0.1 ml of 1M NaOH induced extensive lacrimal gland damage with reduced secretion and scarring in the subconjunctival plane compared to direct cauterization or direct NaOH contact to the ductal orifices of the rabbit lacrimal gland.

Comparative analysis of scaffold fibre diameter-modulated responses on immortalized and primary thyroid cells: Implications for thyroid regeneration

Primary hypothyroidism results from thyroid gland damage, commonly due to radiotherapy for head and neck cancer. Primary hypothyroidism severely impacts patient quality of life and is expected to increase in incidence due to the aging population and rising cancer survivor rates. Tissue engineering approaches are starting to emerge as a potential treatment.Electrospinning techniques have yet to be investigated in conjunction with thyroid tissue. Here, electrospun polycaprolactone scaffolds with varying fibre diameters were fabricated and their effects on immortalized human thyrocytes (Nthy-ori 3–1) and primary murine thyroid cells were investigated. Four groups of scaffolds were produced with fibre diameters ranging from approximately 0.5 µm to 4 µm, to understand the impact of these microenvironments on their potential for thyroid regeneration.Results showed that fibre size influenced mechanical properties, porosity and cell response. Nthy-ori 3–1 cells performed best on the scaffold with medium-sized fibres while primary cells preferred the scaffold with larger fibres. Nonetheless, the scaffold with the smallest fibre diameter encouraged the secretion of collage-like fibrils, potentially indicating favourable conditions for regeneration.This study highlights the potential of electrospun PCL scaffolds as promising candidates for tissue engineering applications in the treatment of primary hypothyroidism. The findings demonstrate the importance of tailoring scaffold properties and considering cell-type specific responses when designing biomaterials for tissue-engineered solutions for thyroid regeneration. Further research is necessary to elucidate the underlying mechanisms and optimize scaffold properties for successful thyroid tissue regeneration.

AS101 regulates the Teff/Treg balance to alleviate rabbit autoimmune dacryoadenitis through modulating NFATc2

Sjögren's syndrome (SS) dry eye can cause ocular surface inflammation and lacrimal gland (LG) damage, leading to discomfort and potential vision problems. The existing treatment options for SS dry eye are currently constrained. We investigated the possible therapeutic effect and the underlying mechanism of AS101 in autoimmune dry eye. AS101 was injected subconjunctivally into a rabbit model of autoimmune dacryoadenitis and its therapeutic effects were determined by evaluating clinical and histological scores. The expressions of effector T cells (Teff)/regulatory T cells (Treg)-related transcription factors and cytokines, inflammation mediators, and transcription factor NFATc2 were measured by quantitative real-time PCR and/or Western blot both in vivo and in vitro. Additionally, the role of NFATc2 in the immunomodulatory effects of AS101 on T cells was explored by co-culturing activated peripheral blood lymphocytes (PBLs) transfected with NFATc2 overexpression lentiviral plasmid with AS101. AS101 treatment potently ameliorated the clinical severity and reduced the inflammation of LG. Further investigation revealed that AS101 treatment led to decreased expression of Th1-related genes (T-bet and IFN-γ) and Th17-related genes (RORC, IL-17A, IL-17F, and GM-CSF) and increased expression of Treg-related gene Foxp3 in vivo and in vitro. Meanwhile, AS101 suppressed the expression of TNF-α, IL-1β, IL-23, IL-6, MMP-2, and MMP-9. Mechanistically, AS101 downregulated the expression of NFATc2 in inflamed LGs. Overexpression of NFATc2 in activated PBLs partially blunted the effect of AS101 on Teff suppression and Treg promotion. In conclusion, AS101 is a potential regulator of Teff/Treg cell balance and could be an effective treatment agent for SS dry eye.

Potential predictive value of IVIM MR for xerostomia in nasopharyngeal carcinoma

Background and PurposeXerostomia, caused by radiation-induced parotid damage, is the most commonly reported radiotherapy (RT) complication for nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the value of intravoxel incoherent motion (IVIM) MR in monitoring radiation-induced parotid gland damage and predicting the risk of xerostomia. MethodsFifty-four NPC patients were enrolled and underwent at least three IVIM MR scans: before (pre-RT), after 5 fractions of (5th-RT), halfway through (mid-RT), and after RT (post-RT). The degree of xerostomia patients was assessed before each MR examination. Furthermore, the time when patients first reported xerostomia symptoms was recorded. The changes in IVIM parameters throughout RT, as well as the relationships between IVIM parameters and xerostomia, were analysed. ResultAll IVIM parameters increased significantly from pre-RT to post-RT (p < 0.001). The rates of D, D* and f increase increased significantly from pre-RT to mid-RT (p < 0.001), indicating that cell necrosis mainly occurs in the first half of RT. In multivariate analysis, N3 (p = 0.014), pre-D (p = 0.007) and pre-D* (p = 0.003) were independent factors influencing xerostomia. D and f were significantly higher at 5th-RT than at pre-RT (both p < 0.05). IVIM detected parotid gland injury at 5th-RT at an average scanning time of 6.18 ± 1.07 days, earlier than the 11.94 ± 2.61 days when the patient first complained of xerostomia according to the RTOG scale (p < 0.001). ConclusionsIVIM MR can dynamically monitor radiation-induced parotid gland damage and assess it earlier and more objectively than RTOG toxicity. Moreover, IVIM can screen people at risk of more severe xerostomia early.

Transareolar Video-Assisted Thoracoscopic Surgery in Females: A Novel Incision for Pulmonary Ground Glass Nodule Resection.

Purpose: Uniportal video-assisted thoracoscopic surgery (VATS) is recognized for its minimally invasive nature, widely adopted globally. However, the evident scarring it leaves often triggers psychological apprehension and resistance to surgery. Transareolar incision, known for its superior cosmetic outcome with no visible scars, poses challenges in women due to the risk of mammary gland damage. In this report, we present successful pulmonary ground glass nodule (GGN) resection using transareolar VATS in female patients, aiming to address these concerns. Materials and Methods: We retrospectively analyzed the clinical data of 35 female patients who underwent GGN resection through transareolar VATS between August 2020 and March 2022. Results: There were no serious complications or perioperative deaths in this cohort of 35 female patients undergoing GGN resection through transareolar VATS. The operations, including local resection or segmentectomy, had an average duration of 70.1 ± 26.4 minutes, with a tube duration of 4.7 ± 2.1 days and a hospitalization time of 7.2 ± 2.3 days. The surgical approach varied, with 21 cases using transareolar uniport, 8 cases assisted by a 3-mm tiny port, and 6 cases converted to two-port VATS. Scar outcomes varied, with 21 cases showing no scar, 8 cases displaying a microscar, and 6 cases presenting a dominant scar of 1.7 ± 0.5 cm. Postoperative pain scores at 1 week and 1 month were 1.9 ± 0.9 and 1.0 ± 0.9, respectively, and the wound numbness occurred in 2.86% (1/35) of cases. Regarding breast complications, 2 patients suffered delayed healing of the incision. No damage and inflammation of glands were detected by breast B-mode ultrasonography. Conclusions: The transareolar incision emerges as a novel approach for VATS in female patients, offering advantages in terms of pain management and cosmetic outcomes.

Cell type-specific transforming growth factor-β (TGF-β) signaling in the regulation of salivary gland fibrosis and regeneration

Salivary gland damage and hypofunction result from various disorders, including autoimmune Sjögren's disease (SjD) and IgG4-related disease (IgG4-RD), as well as a side effect of radiotherapy for treating head and neck cancers. There are no therapeutic strategies to prevent the loss of salivary gland function in these disorders nor facilitate functional salivary gland regeneration. However, ongoing aquaporin-1 gene therapy trials to restore saliva flow show promise. To identify and develop novel therapeutic targets, we must better understand the cell-specific signaling processes involved in salivary gland regeneration. Transforming growth factor-β (TGF-β) signaling is essential to tissue fibrosis, a major endpoint in salivary gland degeneration, which develops in the salivary glands of patients with SjD, IgG4-RD, and radiation-induced damage. Though the deposition and remodeling of extracellular matrix proteins are essential to repair salivary gland damage, pathological fibrosis results in tissue hardening and chronic salivary gland dysfunction orchestrated by multiple cell types, including fibroblasts, myofibroblasts, endothelial cells, stromal cells, and lymphocytes, macrophages, and other immune cell populations. This review is focused on the role of TGF-β signaling in the development of salivary gland fibrosis and the potential for targeting TGF-β as a novel therapeutic approach to regenerate functional salivary glands. The studies presented highlight the divergent roles of TGF-β signaling in salivary gland development and dysfunction and illuminate specific cell populations in damaged or diseased salivary glands that mediate the effects of TGF-β. Overall, these studies strongly support the premise that blocking TGF-β signaling holds promise for the regeneration of functional salivary glands.

Mesenchymal Stromal/Stem Cell Therapy Improves Salivary Flow Rate in Radiation-Induced Salivary Gland Hypofunction in Preclinical in vivo Models: A Systematic Review and Meta-Analysis.

Mesenchymal stromal/stem cells (MSCs) have been suggested for salivary gland (SG) restoration following radio-induced salivary gland damage. This study aimed to determine the safety and effectiveness of MSC therapy on radio-induced SG damage and hypofunction in preclinical in vivo studies. PubMed and EMBASE were systematically searched for preclinical in vivo interventional studies evaluating efficacy and safety of MSC treatment following radio-induced salivary gland damage published before 10th of January 2022. The primary endpoint was salivary flow rate (SFR) evaluated in a meta-analysis. The study protocol was published and registered on PROSPERO ( www.crd.ac.uk/prospero ), registration number CRD42021227336. A total of 16 preclinical in vivo studies were included for qualitative analysis (858 experimental animals) and 13 in the meta-analysis (404 experimental animals). MSCs originated from bone marrow (four studies), adipose tissue (10 studies) and salivary gland tissue (two studies) and were administered intravenously (three studies), intra-glandularly (11 studies) or subcutaneously (one study). No serious adverse events were reported. The overall effect on SFR was significantly increased with a standardized mean difference (SMD) of 6.99 (95% CI: 2.55-11.42). Studies reported improvements in acinar tissue, vascular areas and paracrine factors. In conclusion, this systematic review and meta-analysis showed a significant effect of MSC therapy for restoring SG functioning and regenerating SG tissue following radiotherapy in preclinical in vivo studies without serious adverse events. MSC therapy holds significant therapeutic potential in the treatment of radio-induced xerostomia, but comprehensive, randomized, clinical trials in humans are required to ascertain their efficacy in a clinical setting.

Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin.

Radiation triggers salivary gland damage and excess iron accumulates in tissues induces cell injury. Flavonoids are found in some fruits and are utilized as potent antioxidants and radioprotective agents. This study aimed to evaluate the antioxidant and anti-inflammatory effects of hesperidin and rutin on gamma radiation and iron overload induced submandibular gland (SMG) damage and to evaluate their possible impact on mitigating the alteration in mTOR signaling pathway and angiogenesis. Forty-eight adult male Wistar albino rats were randomly assigned to six groups: group C received a standard diet and distilled water; group H received hesperidin at a dose of 100mg/kg; four times a week for four weeks; group U received rutin at a dose of 50mg/kg; three times a week for three weeks; group RF received a single dose (5Gy) of gamma radiation followed by iron at a dose of 100mg/kg; five times a week for four weeks; group RFH received radiation and iron as group RF and hesperidin as group H; group RFU received radiation and iron as group RF and rutin as group U. SMG specimens from all groups were removed at the end of the experiment; and some were used for biochemical analysis, while others were fixed for histological and immunohistochemical examination. In the RF group, several genes related to antioxidants (Nrf-2 and SOD) and DNA damage (BRCA1) were significantly downregulated, while several genes related to inflammation and angiogenesis (TNFα, IL-1β and VEGF) and the mTOR signaling pathway (PIK3ca, AKT and mTOR) were significantly upregulated. Acinar cytoplasmic vacuolation, nuclear pyknosis, and interacinar hemorrhage with distinct interacinar spaces were observed as histopathological changes in SMGs. The duct system suffered significant damage, eventually degenerating entirely as the cells were shed into the lumina. VEGF and NF-κB were also significantly overexpressed. Hesperidin and rutin cotreatment generated partial recovery as indicated by significant upregulation of Nrf-2, SOD and BRCA1 and considerable downregulation of TNF-α, IL-1β, VEGF, PIK3ca, AKT, and mTOR. Although some acini and ducts continued to deteriorate, most of them had a normal appearance. There was a notable decrease in the expression of VEGF and NF-κB. In γ-irradiated rats with iron overload, the administration of hesperidin and rutin may mitigate salivary gland damage.

Combining Runmu fengye tang preparation with hydroxysugar glycolic acid eye drops regulates Th17/Treg balance to treat dry eyes via inhibition of JAK2/STAT3 pathway

Purpose: To determine effective therapies for the prevention and clinical treatment of dry eye.&#x0D; Methods: A scopolamine-induced dry eye rabbit model was administrated with Runmu Fengliang tang (RMFS) and hypromellose 2910, dextran 70 and glycerol eye drops (HGA). Schirmer's I test (SIt), break-up time (BUT) and histopathologic examinations (H&amp;E) were used to assess dry eye symptoms and lacrimal gland damage. Flow cytometry was used to determine the number of apoptotic cells and percentages of Th17 and Treg, while Western blot assay was used to evaluate the expression of proteins related to JAK2/STAT3 pathway.&#x0D; Results: The combination of RMFS with HGA significantly increased tear secretion (p &lt; 0.001), shortened tear break-up time (p &lt; 0.001), repaired ocular surface damage and reduced apoptosis (p &lt; 0.05) in the scopolamine-induced dry eye model in rabbits, compared with the single-administration group. In addition, it regulated the Th17/Treg-related cytokine balance and inhibited the JAK2/SATA3 pathway.&#x0D; Conclusion: The combination of RMFS and HGA alleviate dry eye symptoms by inhibiting the JAK2/SATA3 pathway in model rabbits induced by scopolamine and this treatment could be a potential therapeutic strategy for the treatment of dry eye disease. Future studies should focus on clinical data collection to investigate the efficacy and safety of the combination.