From Likes to Saving Lives: Embracing Social Media's Power to Connect, Learn, and Innovate in Medical Education Delivery.

Social media have become an integral part of human life, because the manner in which we communicate, share information, and network with the external world is changing significantly. The purpose of the current review is to explore the role of social media in transforming medical education, identify the merits and the potential concerns, and propose effective strategies to overcome the identified challenges. Social media have significant potential in strengthening the delivery of medical education and meeting the scenarios emerging out of changing dynamics. The most important aspect of social media is that they have global reach and wide accessibility, and promotes active engagement of students. Similar to any other teaching-learning method, even the use of social media has its own limitations-cum-concerns. We must come out with potential solutions to each one of these problems so that overall acceptance and utilization of social media applications can be optimized. In conclusion, social media in medical education have immense potential to revolutionize learning and provide a platform for collaborative learning and networking. The need of the hour is to do systematic planning, train stakeholders, and establish guidelines for promoting effective engagement while using social media, and thereby keeping pace with the rapidly evolving healthcare landscape.

Pharmacological inhibition of the LIF/LIFR autocrine loop reveals vulnerability of ovarian cancer cells to ferroptosis.

Of all gynecologic cancers, epithelial-ovarian cancer (OCa) stands out with the highest mortality rates. Despite all efforts, 90% of individuals who receive standard surgical and cytotoxic therapy experience disease recurrence. The precise mechanism by which leukemia inhibitory factor (LIF) and its receptor (LIFR) contribute to the progression of OCa remains unknown. Analysis of cancer databases revealed that elevated expression of LIF or LIFR was associated with poor progression-free survival of OCa patients and a predictor of poor response to chemotherapy. Using multiple primary and established OCa cell lines or tissues that represent five subtypes of epithelial-OCa, we demonstrated that LIF/LIFR autocrine signaling is active in OCa. Moreover, treatment with LIFR inhibitor, EC359 significantly reduced OCa cell viability and cell survival with an IC50 ranging from 5-50 nM. Furthermore, EC359 diminished the stemness of OCa cells. Mechanistic studies using RNA-seq and rescue experiments unveiled that EC359 primarily induced ferroptosis by suppressing the glutathione antioxidant defense system. Using multiple in vitro, ex vivo and in vivo models including cell-based xenografts, patient-derived explants, organoids, and xenograft tumors, we demonstrated that EC359 dramatically reduced the growth and progression of OCa. Additionally, EC359 therapy considerably improved tumor immunogenicity by robust CD45+ leukocyte tumor infiltration and polarizing tumor-associated macrophages (TAMs) toward M1 phenotype while showing no impact on normal T-, B-, and other immune cells. Collectively, our findings indicate that the LIF/LIFR autocrine loop plays an essential role in OCa progression and that EC359 could be a promising therapeutic agent for OCa.

Peptidomics-based identification of antihypertensive and antidiabetic peptides from sheep milk fermented using Limosilactobacillus fermentum KGL4 MTCC 25515 with anti-inflammatory activity: in silico, in vitro, and molecular docking studies.

This study investigated the synthesis of bioactive peptides from sheep milk through fermentation with Limosilactobacillus fermentum KGL4 MTCC 25515 strain and assessed lipase inhibition, ACE inhibition, α-glucosidase inhibition, and α-amylase inhibition activities during the fermentation process. The study observed the highest activities, reaching 74.82%, 70.02%, 72.19%, and 67.08% (lipase inhibition, ACE inhibition, α-glucosidase inhibition, and α-amylase inhibition) after 48 h at 37°C, respectively. Growth optimization experiments revealed that a 2.5% inoculation rate after 48 h of fermentation time resulted in the highest proteolytic activity at 9.88 mg/mL. Additionally, fractions with less than 3 kDa of molecular weight exhibited superior ACE-inhibition and anti-diabetic activities compared to other fractions. Fermentation of sheep milk with KGL4 led to a significant reduction in the excessive production of NO, TNF-α, IL-6, and IL-1ß produced in RAW 267.4 cells upon treatment with LPS. Peptides were purified utilizing SDS-PAGE and electrophoresis on 2D gels, identifying a maximum number of proteins bands ranging 10-70 kDa. Peptide sequences were cross-referenced with AHTPDB and BIOPEP databases, confirming potential antihypertensive and antidiabetic properties. Notably, the peptide (GPFPILV) exhibited the highest HPEPDOCK score against both α-amylase and ACE.

Large atypical lipomatous tumour of the neck with mediastinal extension managed by transcervical excision.

Tumours of adipose tissue origin are relatively rare in the head and neck. Here, we report a case of an unfamiliar lipomatous lesion that involved the neck and mediastinum. A nil-comorbid man in his 40s presented with a slowly progressive anterior neck swelling of 3 years, which was diagnosed as lipoma by histopathological sampling. Computed tomography demonstrated the lesion to be involving parapharyngeal and retropharyngeal spaces with mediastinal extension. The lesion was removed by the transcervical approach. The final histology of the excised specimen, with immunohistochemistry for mouse double minute 2 (MDM2) and p16, suggested an atypical lipomatous tumour (ALT). This report accentuates the occurrence of this rare neoplasm in the neck, which often mimics lipoma clinically. Although radiology can demonstrate suggestive features, histology with MDM2 and/or p16 positivity can confirm the diagnosis of ALT as against the lipoma. A successful transcervical excision, despite the deeper extension of the lesion between the critical structures of the neck and mediastinum, demonstrates the non-infiltrating nature of the tumour.

A Successful Pregnancy Following Intracytoplasmic Sperm Injection in a Breast Cancer Survivor: A Case Report.

This report documents the case of a 36-year-old female diagnosed with stage I invasive ductal carcinoma of the left breast who, alongside her 39-year-old husband, sought fertility assistance at our center due to primary infertility. Having survived cancer twice in the span of their seven-year marriage, the couple faced the challenge of overcoming both the repercussions of cancer treatment and difficulties in conceiving. Initial attempts through three intrauterine insemination (IUI) cycles proved unsuccessful, leading the couple to opt for in vitro fertilization (IVF). The fertility assessment of the husband revealed the presence of several pus cells and a high sperm DNA fragmentation index (DFI). To address this, a medication regimen was administered to improve sperm quality. Concurrently, the female underwent controlled ovarian stimulation (COS) with the anti-estrogen agent letrozole to mitigate the risk of estrogen surges that could compromise her health. Subsequently, oocytes were retrieved from the female, and intracytoplasmic sperm injection (ICSI) was used to facilitate fertilization with her husband's sperm. Following successful embryo development, the patient underwent embryo transfer (ET), resulting in a positive beta-human chorionic gonadotropin (beta-hCG) result, signifying a successful conception. This case report highlights the intricate challenges faced by individuals with a history of breast cancer, emphasizing the delicate balance required in managing infertility in such circumstances. The described approach, involving personalized treatments and meticulous care, underscores the possibility of achieving successful conception for females struggling with fertility issues post-cancer survival. The documented journey serves as a testament to the resilience of individuals facing the dual challenges of cancer survival and infertility, offering insights into the complexities of their reproductive healthcare.

An Unusual High Bifurcation of the Brachial Artery: A Cadaveric Case Report.

The human vascular system exhibits a remarkable degree of anatomical variability, with deviations from conventional arterial branching patterns occasionally encountered. Among these variations, the atypical bifurcation has drawn attention for its infrequent occurrence and potential clinical implications. This study investigates the rare anatomical variation of high bifurcation seen during cadaver dissection in the brachial artery. It emphasizes the relevance of understanding such variations in established vascular anatomy and their clinical implications. Detailed findings from the dissection of the upper limbs, which reveal a high bifurcation in a 40-year-old male cadaver, are presented. The report highlights unique anatomical variations, including a superficial path. The conclusion underscores the rarity of this high bifurcation and its potential impact on medical procedures. It stresses the importance of healthcare professionals being aware of and prepared for such anatomical variations for optimal patient care. In order to manage potential difficulties during medical operations affecting the circulatory system and eventually enhance patient outcomes, it is necessary to understand these deviations.

A Comprehensive Approach to Polycystic Ovarian Syndrome: A Case Report of Successful Intracytoplasmic Sperm Injection Treatment Utilizing the Short Antagonist Protocol and Hatching.

The 29-year-old participant in the case study has been grappling with infertility for the last six years. Following an assessment of her symptoms, hormone profile, and ultrasound results, she received a diagnosis of polycystic ovarian syndrome (PCOS). PCOS is a multifaceted endocrine and metabolic disorder characterized by symptoms such as obesity, insulin resistance, anovulation, and polycystic ovaries. Various factors, including heredity, intestinal dysbiosis, obesity, environmental pollutants, lifestyle choices, and neuroendocrine abnormalities, contribute to the susceptibility of women to PCOS. In planning polycystic ovarian stimulation, it is crucial to consider parameters such as antral follicle count (AFC), luteinizing hormone (LH), and anti-Müllerian hormone (AMH). Careful planning of the gonadotrophin dose is essential to achieve an optimal response during a gonadotropin-releasing hormone antagonist (GnRH-ant) cycle. In our case, the brief antagonist protocol was used, resulting in a favorable outcome with minimal risk of ovarian hyperstimulation syndrome (OHSS). Despite multiple unsuccessful attempts at natural conception, the patient successfully conceived with the help of intracytoplasmic sperm injection (ICSI), leading to a positive pregnancy outcome. In addition to incorporating mechanical hatching to promote implantation, we diligently selected the most beneficial medications for the patient.

Association Between Foramen Rotundum and Trigeminal Neuralgia in the Saudi Population: A Radiological Study.

The trigeminal nerve is responsible for transmitting sensory information from the face, nasal and mouth cavities, and most of the scalp. Trigeminal neuralgia (TN) is a chronic facial pain disorder characterized by spontaneous paroxysmal pain throughout the distribution of the trigeminal nerve. This study investigated the morphological and morphometric variations of the foramen rotundum (FR) and its association with TN through a retrospective radiological analysis. A cohort of 97 participants from King Fahad University Hospital, Saudi Arabia, comprising 57 TN patients and 40 controls, underwent head CT scans for measurement and analysis. The study revealed significant differences in the FR morphology between TN patients and controls, particularly noting narrower FR measurements among TN individuals, especially in females. The right side demonstrated narrower FR dimensions, potentially correlating with the predominant side of pain in TN patients. While the presence of bony spurs was absent in all participants, variations in FR shape, size, and spatial positioning were observed and compared across genders and groups. These findings provide crucial insights into the potential anatomical factors contributing to TN, emphasizing the importance of understanding FR variations in clinical assessment and management of TN cases. Further research focusing on FR morphology and its clinical implications is recommended to enhance understanding and aid medical professionals in addressing TN-related concerns.

Morphometric Parameters of the Ear and Their Sexual Dimorphism in the Eastern Province of Saudi Arabia.

Background The human ear is a distinctive facial feature, revealing valuable information about ethnicity, gender, and age. Anthropometric measures play a crucial role in fields such as forensic medicine, prosthetics, and plastic surgery. The external ear, known for its diversity in structure and individual characteristics, has become a subject of interest in various populations. This study aims to determine the mean values of morphometric measurements for both right and left ears while exploring sexual dimorphism in ear dimensions. Methodology A prospective, observational, cross-sectional study was conducted among 200 volunteers from the eastern province of Saudi Arabia, comprising 98 males and 102 females, at the Department of Anatomy, Institute of Medical Sciences, Imam Abdulrahman Bin Faisal University. Participants were randomly selected from King Fahad University Hospital workers and patients. Using a Vernier caliper and after obtaining consent, various aspects of ear morphology were measured. The study employed statistical analyses such as the volunteers' t-test, Pearson's coefficient of correlation, and linear regression equations. Results In males, the mean total height of the right and left ears was 6.054 ± 0.5394 and 6.044 ± 0.5235 cm, respectively, while for females, it was 5.489 ± 0.4481 and 5.763 ± 4.8446 cm, respectively. The mean widths, heights, and other dimensions of the ears exhibited variations between genders. Conclusions The study provides comprehensive insights into the dimensions and indices of the pinna among the population of the eastern province of Saudi Arabia. The findings confirmed the presence of sexual dimorphism in the ear measurements, consistent with observations in other ethnic groups.

The Potential of Theophylline and Pentoxifylline in Sperm Optimization and Its Intracytoplasmic Sperm Injection Outcomes.

Sperm motility is an essential selection criteria by embryologists at the time of intracytoplasmic sperm injection (ICSI). One method of testing sperm viability is to induce sperm motility by increasing cyclic adenosine monophosphate (cAMP) levels by treating a semen sample with phosphodiesterase inhibitors (PDEIs), such as theophylline and pentoxifylline. It explores the implications of PDEI in medical care, reflecting on its effects in clinical settings and recognizing potential topics for future exploration. This analysis revealed that by incorporating stimulants that activate movements, the time it took to single out sperms was markedly reduced, and consequently, the sperms were safeguarded from a prolonged period of oxidative stress. Furthermore, theophylline was found to advance sperm motility, consequently resulting in several initially immobile spermatozoa displaying rapid progressive motility. Higher fertilization rate, cleavage rate, good quality embryos (grade I), and higher biochemical and clinical pregnancy rates were found with artificial sperm activation (ASA) using pentoxifylline and theophylline. This review emphasizes the need for more research to evaluate the drug's long-term safety and investigate the effects of theophylline and pentoxifylline on postfertilization parameters, such as embryo development, implantation, and pregnancy outcomes. These areas of investigation are important for understanding the complete impact of these agents and to ensure their safe and effective implementation in clinical practice.

Flipped Classrooms in Medical Education: Improving Learning Outcomes and Engaging Students in Critical Thinking Skills.

The flipped classroom (FC) model involves students independently acquiring knowledge before in-person class sessions, during which they engage in active discussions and problem-solving. Various methods to implement FC are quizzes, e-content, case-based learning, problem-based learning, and reading assignments. The advantages of the FC approach included improved student preparation, active participation, and the promotion of critical thinking skills. Some disadvantages identified are technical problems like internet connection, improper planning and preparation, which increases teacher workload, and lack of self-motivation. This review underscores the potential of the FC approach to improve medical education by promoting independent learning, active participation, and deeper understanding. Consideration of factors such as curriculum design, faculty development, technological infrastructure, and student readiness is vital for successfully implementing the FC model. Balancing self-directed study with meaningful face-to-face interactions remains crucial to harnessing the full benefits of this innovative approach. By leveraging technology and student-centered methods, medical educators can create an enriched learning experience that positively influences future healthcare professionals.

A Review of Amelioration of Awareness About Blood Donation Through Various Effective and Practical Strategies.

Blood donations play a crucial role in medical care; however, the global shortage of donors remains and has a serious impact on medical interventions. The challenges involved include the lack of public awareness of the importance of blood donation, the lack of understanding of the process and eligibility criteria for blood donation, and the lack of comprehensive strategies aimed at raising awareness and participation among potential donors, with particular emphasis on the involvement of young people. It is essential to recognize that blood donation delivers significant benefits to donors and recipients, improves overall health, and ultimately saves lives. Various initiatives, such as blood donation camps, dynamic social media campaigns, and strategic networking of medical professionals, have proved effective in promoting blood donation. In particular, in the event of an emergency, the availability of sufficient blood supplies is increasingly essential, underlining the urgent need to establish and maintain a sustainable blood donor network. An in-depth understanding of the motivation and conservation of donors is crucial in this context, as it is known that demographic factors significantly impact the frequency of blood donation. In addition, ethical and legal considerations require careful attention, highlighting the essential role of obtaining informed consent and ensuring the confidentiality of donors throughout the process. As we look ahead to the evolving landscape, it presents a series of formidable challenges. These challenges encompass the critical necessity to broaden and diversify our donor base, thereby extending and varying our sources of financial support for specific initiatives, organizations, or projects. Moreover, we must proactively harness the opportunities presented by emerging technologies and commit ourselves to closing the information gaps within the existing public knowledge sphere. In summary, the review emphasizes the paramount importance of ongoing efforts to strengthen and enrich donors' engagement through customized strategies and educational outreach.

Probiotic potential of gluten degrading Bacillus tequilensis AJG23 isolated from Indian traditional cereal-fermented foods as determined by Multiple Attribute Decision-Making analysis.

The present study reported the characterization of gluten hydrolyzing strains of Bacillus sp. from fermented cereal dough. The strains were characterized for probiotic as well as technological attributes. A total of 45 presumptive gluten degrading isolates were obtained on gliadin agar plate assay. Based on hemolytic and antibiotic susceptibility pattern, only six isolates were considered safe which also indicated gliadinase activity on zymography. All the six strains were able to resist the pH 2.0, 0.25% bile and also possessed ability to adhere to the organic solvents and mucin. The cell free supernatant of five strains exhibited antimicrobial activities against Gram-positive and Gram-negative pathogens. A more than 50% survival of the isolated strains was obtained at a salt concentration of 2%, phenol concentration of 0.1% and temperature upto 45 °C. All the strains exhibited antioxidant activities and biofilm forming ability. Furthermore, the ranking of strains based on probiotic as well as other functional attributes was determined using multidimensional Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). A matrix of multidimensional indicators was prepared using alternatives and criteria, the analysis indicated the strain Bacillus tequilensis AJG23 as the potential probiotic candidate based on all screening criteria. Further work still needs to be done about the protective role of the potential strain against gluten sensitivity using in vitro models.

Managing Diabetes Mellitus With Millets: A New Solution.

Diabetes mellitus (DM) is the leading cause of morbidity and mortality, and the disease's prevalence is increasing with each passing day. DM can be prevented and controlled with modifications to the diet, especially by incorporating millet in the diet. Throughout history, eating habits have been recognized for their significant contribution to promoting health and wellness by eating foods rich in nutrients. Millet is an underutilized food crop with many benefits for health, with the most beneficial being low glycemic index, high fiber content, polyunsaturated fatty acids (PUFA), non-acid-forming potential, and gluten-free. In addition to staple food crops, such as wheat, rice, and foxtail millet, millets are still highly nutritious and beneficial and have great potential to help the world combat the food insecurity many countries face today. Millets are in the top positions of recommended dietary charts with their numerous health benefits and antioxidant properties.

Metformin-induced activation of Ca2+ signaling prevents immune infiltration/pathology in Sjogren's syndrome-prone mouse models.

Immune cell infiltration and glandular dysfunction are the hallmarks of autoimmune diseases such as primary Sjogren's syndrome (pSS), however, the mechanism(s) is unknown. Our data show that metformin-treatment induces Ca2+ signaling that restores saliva secretion and prevents immune cell infiltration in the salivary glands of IL14α-transgenic mice (IL14α), which is a model for pSS. Mechanistically, we show that loss of Ca2+ signaling is a major contributing factor, which is restored by metformin treatment, in IL14α mice. Furthermore, the loss of Ca2+ signaling leads to ER stress in salivary glands. Finally, restoration of metformin-induced Ca2+ signaling inhibited the release of alarmins and prevented the activation of ER stress that was essential for immune cell infiltration. These results suggest that loss of metformin-mediated activation of Ca2+ signaling prevents ER stress, which inhibited the release of alarmins that induces immune cell infiltration leading to salivary gland dysfunction observed in pSS.

The Role of E-Content Development in Medical Teaching: How Far Have We Come?

With the advancements in technology, medical educators are now able to create and deliver content to students through digital platforms. Electronic content (e-content) development has allowed educators to incorporate multimedia, animations, simulations, and interactive elements which support verbal instruction, such as improved expression and comprehension, into their teaching materials. E-content development is a relatively new field, but it is growing very rapidly. Recent findings have indicated that the e-learning sector will likely experience a huge surge in the upcoming years. The Indian government has launched various initiatives for e-content development in medical education. E-content development has great potential and can be used in various learning scenarios. While it initially gained popularity in higher education, it has since been applied to many other sectors, including healthcare. It allows educators to create highly engaging learning experiences that are accessible by all students. Challenges in e-content development include availability of the internet, creating content that is engaging and relevant to a wide range of learners, and access. Still, it is expected that the use of e-content in medical teaching will continue to increase in the future. The future of e-content development in medical teaching is likely to see continued growth and innovation as technology advances and more educators and learners recognize the benefits of online and digital resources.

Assessment of dental student education and preparedness in periodontics in two different models: Discipline-based and general practice-based learning.

PURPOSE: To compare dental students' preparedness in clinical periodontal education following their participation in a discipline-based predoctoral periodontics clinic with dental students that received a general practice-based periodontal education. METHODS: 114 third-year dental students and 112 fourth-year dental students at the University of Texas Health Science Center in San Antonio, were emailed an online survey consisting of questions on their proficiency and confidence levels in diagnosing periodontal diseases and conditions, treatment planning, performing non-surgical periodontal treatment, identifying the need for referral, and their perceived impediments on their clinical periodontics education. RESULTS: Approximately 97% of third-year dental students that participated in discipline-based predoctoral periodontics agree that they are overall confident in providing excellent periodontal care to their patients, and 91% of these students feel that their participation in the predoctoral periodontics clinic has enhanced their knowledge in periodontics as well as their confidence level when providing periodontal patient care. While 95% of fourth-year dental students agree that they feel confident in providing excellent periodontal care to their patients, only 83% felt that level of confidence during their third-year in dental school, and 77% believe that given the option to participate in the pre-doctoral periodontics clinic, their periodontal education would have been strengthened. CONCLUSIONS: Our results show that the integration of a discipline based predoctoral periodontics clinic has benefited the dental students and boosted their knowledge and confidence in diagnosing and treating periodontal patients. This model can be improved by addressing space and time limitations.

Optimized feature fusion-based modified cascaded kernel extreme learning machine for heart disease prediction in E-healthcare.

In recent years, medical technological innovators have focused on diverse clinical therapies to find innovative ways to overcome clinical challenges. But still, there emerge certain drawbacks like high computational cost, increased error, less training ability, the requirement of high storage space and degraded accuracy. To conquer these drawbacks, the proposed research article presents an innovative cascaded extreme learning machine for effective heart disease (HD) prediction. Missing data filtering and normalization methods are carried out for data pre-processing. From the pre-processed data, the features are extracted using the Framingham risk factor extraction module, whereas the extracted features are fused to generate a feature vector. The most significant features are selected using Rhino Satin Herd optimization algorithm. Using a linear weight assignment approach, the feature weighting process is undertaken by allocating higher weights to significant features and less weight to unwanted features. Finally, classification is performed through the Cascaded kernel soft plus extreme learning machine with a stacked autoencoder model. The performance is analyzed using PYTHON to evaluate the superiority of the proposed model. The proposed model obtained an overall accuracy of 90%, precision of 94%, recall of 91.3% and F1 measure of 92.6% in the Cleveland-Hungarian dataset, which is comparatively superior to the existing methods. An accuracy of 92.6% is attained for predicting HD in terms of the heart patient dataset. The proposed model attains better performance because of effective accuracy outcome, reduced overfitting issues, fewer error rates, better convergence and training ability.

Ablation of TRPC3 disrupts Ca2+ signaling in salivary ductal cells and promotes sialolithiasis.

Clinical studies and structural analyses of salivary stones strongly suggest a linkage between higher saliva calcium (Ca2+) and salivary stone formation, sialolithiasis; however, the process and the mechanism leading to Ca2+ overload during sialolithiasis is not well understood. Here, we show that TRPC3 null (-/-) mice presented with a reduction in Ca2+ entry and current in ductal cells with higher saliva [Ca2+] suggesting diminished transepithelial Ca2+ flux across the salivary ductal cells, leaving more Ca2+ in ductal fluid. Significantly, we found that TRPC3 was expressed in mice and human salivary ductal cells, while intraductal stones were detected in both mice (TRPC3-/-) and patient (sialolithiasis) salivary glands. To identify the mechanism, we found that TRPC3 was crucial in preventing the expression of calcification genes (BMP2/6, Runx2) in ductal cells which may be due to higher extracellular Ca2+ in SMG tissues. Similarly, inflammatory (IL6, NLRP3), fibrotic (FN1, TGFß1) and apoptotic (Bax1/Bcl2) markers were also elevated, suggesting that the loss of TRPC3 induces genetic changes that leads to salivary gland cell death and induction of inflammatory response. Overall, ablation of TRPC3-/- leads to higher saliva [Ca2+], along with elevated detrimental gene expressions, altogether contributing to salivary gland stone formation.

Targeting alarmin release reverses Sjogren's syndrome phenotype by revitalizing Ca2+ signalling.

BACKGROUND: Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that is embodied by the loss of salivary gland function and immune cell infiltration, but the mechanism(s) are still unknown. The aim of this study was to understand the mechanisms and identify key factors that leads to the development and progression of pSS. METHODS: Immunohistochemistry staining, FACS analysis and cytokine levels were used to detect immune cells infiltration and activation in salivary glands. RNA sequencing was performed to identify the molecular mechanisms involved in the development of pSS. The function assays include in vivo saliva collection along with calcium imaging and electrophysiology on isolated salivary gland cells in mice models of pSS. Western blotting, real-time PCR, alarmin release, and immunohistochemistry was performed to identify the channels involved in salivary function in pSS. RESULTS: We provide evidence that loss of Ca2+ signaling precedes a decrease in saliva secretion and/or immune cell infiltration in IL14α, a mouse model for pSS. We also showed that Ca2+ homeostasis was mediated by transient receptor potential canonical-1 (TRPC1) channels and inhibition of TRPC1, resulting in the loss of salivary acinar cells, which promoted alarmin release essential for immune cell infiltration/release of pro-inflammatory cytokines. In addition, both IL14α and samples from human pSS patients showed a decrease in TRPC1 expression and increased acinar cell death. Finally, paquinimod treatment in IL14α restored Ca2+ homeostasis that inhibited alarmin release thereby reverting the pSS phenotype. CONCLUSIONS: These results indicate that loss of Ca2+ signaling is one of the initial factors, which induces loss of salivary gland function along with immune infiltration that exaggerates pSS. Importantly, restoration of Ca2+ signaling upon paquinimod treatment reversed the pSS phenotype thereby inhibiting the progressive development of pSS.