Oral health policies to mitigate the global burden of noncommunicable disease typically advocate for effective workforce policies. However, actions on oral healthcare are often unclear and disengaged from other health policies. This review investigates evidence of the oral health workforce, identifies challenges, possible solutions, and calls for a reformation to mitigate the burden of oral diseases. International reports and related literature were searched and reviewed using a realistic approach focused on the global oral and general health workforces. Dental professions almost everywhere are only peripherally involved in primary care, and dental workforces are sustained with much disparity typically by addressing dentist-to-population ratios without much attention to the realistic needs of communities. Effectiveness is hindered by insufficient interdisciplinary team-care, restricted scope of service, vaguely conceived essential oral care, expensive clinical education, and general misdirection of services. Calls for reform include: (1) identifying key local advocates for reform, including academics, community-based organisations, healthcare providers, and politicians; (2) analysing disparities of essential oral care needs and resources, and implementing necessary changes to local healthcare systems; (3) financing accessible oral care; (4) fostering equity and universal health coverage through cultural sensitivity and interdisciplinary teamwork; (5) clarifying scopes of practice, accreditation standards, and legal foundations for team-care; (6) identifying educational gaps in workforces; (7) promoting reduction of student debt; (8) supporting culturally diverse education for disadvantaged communities; (9) improving quality and accessibility of care; and (10) realistically planning workforce needs based on local estimates of essential needs.
This cross-sectional survey aimed to assess oral health in patients with inflammatory bowel diseases (IBD) living in Austria. Data collection was conducted with an online questionnaire, including when possible validated tools, covering general medical history, socioeconomic factors, IBD-related parameters, and various oral health parameters, that is, tooth loss rate, prevalence of severe periodontitis, oral health-related quality of life (OHRQoL), and presence of oral lesions. The questionnaire was disseminated to the members of the Austrian Crohn's Disease/Ulcerative Colitis Association. The analysis included the responses of 327 patients (68% female; average age 46 years), 134 with ulcerative colitis (UC) or IBD unclassified, and 193 with Crohn's disease (CD). Based on self-reported data, about 85% of the patients reported intake of an IBD-related medication and about two thirds of the responders reported some IBD activity in the past 12 months. Approximately 24% of the patients had < 20 remaining teeth, 34% had severe periodontitis, and 7% reported poor OHRQoL. IBD diagnosis did not affect the odds for having < 20 teeth or self-reported severe periodontitis, but patients with CD presented more frequently with poor OHRQoL. In addition, patients with CD received more frequently information from their physician on the possibility of oral lesions due to IBD; however, > 50% of all patients indicated not having any problems with oral lesions. Oral health remains inadequately addressed in patients with IBD despite the significant need for dental care. Hence, treating physicians should motivate patients with IBD to inform their dentist about their diagnosis and to maintain regular dental checkups.
The blood-retinal barrier (BRB) consists of the inner and outer blood-retinal barrier (abbreviated as inner BRB and outer BRB). The inner and outer BRB's together regulate the transport of substances between the blood and neural retina via various membrane transporters. To utilize the oral administration for the pharmacotherapy of retinal diseases, it is necessary and important to understand many drug transport mechanisms in the BRB's. This review discusses the BRB transport research reported over more than a quarter of a century, particularly the development of in vitro and in vivo transport evaluation systems as well as newly discovered BRB-specific cationic drug transport mechanisms.
Autoimmune blistering diseases (AIBDs) are characterized by autoantibody-mediated epithelial damage affecting the skin and mucous membranes. Among them, pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP) frequently involve the gingiva, most commonly presenting as desquamative gingivitis (DG). This chronic and painful gingival involvement may compromise oral hygiene and favor secondary inflammatory changes. Consequently, growing interest has focused on the periodontal status of patients with AIBDs and on associated oral microbiological findings. A narrative review was conducted using PubMed and Scopus to identify primary studies evaluating periodontal status in patients with AIBDs. Periodontal conditions were mainly assessed using conventional clinical parameters, including probing depth and clinical attachment loss, along with additional periodontal and oral hygiene indices. Ten studies met the inclusion criteria. Most of them reported significantly worse periodontal status in AIBD compared to controls or DG-unaffected sites. In MMP, disease activity, duration, and DG involvement were associated with poorer periodontal parameters. Notably, adjusting for oral hygiene, as performed in only one study, rendered differences in PD and CAL non-significant, suggesting a potential confounding effect. However, the available evidence remains insufficient to support an independent link with clinically defined periodontitis. Only one study applied the 2017 World Workshop periodontitis classification, with similar conclusions. Microbiological data, limited to three MMP studies with heterogeneous methodologies, frequently detect periodontal pathogens associated with inflammatory tissue damage. Patients with AIBD tend to present worse periodontal status, likely due to pain limited oral hygiene and dysbiotic biofilms. These pathogens may amplify inflammation and perpetuate tissue destruction. Nevertheless, microbial profiles appear dynamic and influenced by disease activity and treatment. Recognizing this association is essential for early diagnosis and interdisciplinary management.
A 1-year-old Maine coon cat was presented with acute onset of central vestibular syndrome and recurrent generalized tonic-clonic seizures. Computed tomographic imaging of the head revealed a left-sided intracranial lesion consistent with an abscess, associated with bilateral otitis media/interna, with more severe involvement of the left tympanic bulla. Based on clinical and imaging findings, the cat underwent surgical intervention consisting of a left temporal burr-hole craniotomy for abscess drainage combined with a unilateral ventral bulla osteotomy. Purulent material was collected during surgery and submitted for bacterial culture, which yielded Staphylococcus aureus sensitive to amoxicillin-clavulanic acid and metronidazole. Postoperative management included intravenous antimicrobial therapy followed by oral treatment after discharge. Transient vestibular dysfunction and Horner's syndrome were observed after surgery and resolved completely within 3 mo. At a long-term follow-up, the cat was neurologically normal. This case highlights the successful surgical management of an otogenic intracranial abscess in a cat and supports unilateral surgical treatment guided by clinical and imaging findings. Key clinical message: Intracranial abscesses secondary to otogenic infection should be considered in cats that have central vestibular clinical signs and seizures. A combined surgical approach using burr-hole craniotomy and ventral bulla osteotomy, guided by imaging findings, can result in favorable clinical outcomes. Abcès intracrânien et otite interne traités par craniotomie par trépanation temporale et ostéotomie de la bulle tympanique ventrale chez un chat Maine CoonUn chat Maine Coon âgé de 1 an a été présenté pour un syndrome vestibulaire central d’apparition brutale et des crises tonico-cloniques généralisées récurrentes. La tomodensitométrie cérébrale a révélé une lésion intracrânienne gauche compatible avec un abcès, associée à une otite moyenne/interne bilatérale, avec une atteinte plus sévère de la bulle tympanique gauche. Compte tenu des résultats cliniques et d’imagerie, le chat a subi une intervention chirurgicale consistant en une craniotomie par trépanation temporale gauche pour le drainage de l’abcès, associée à une ostéotomie unilatérale de la bulle tympanique ventrale. Le liquide purulent prélevé pendant l’intervention a été mis en culture, révélant la présence de Staphylococcus aureus sensible à l’amoxicilline-acide clavulanique et au métronidazole. La prise en charge postopératoire a consisté en une antibiothérapie intraveineuse, suivie d’un traitement oral après la sortie de l’hôpital. Un dysfonctionnement vestibulaire transitoire et un syndrome de Horner ont été observés après l’intervention chirurgicale et ont disparu complètement en 3 mois. Lors d’un suivi à long terme, le chat présentait un examen neurologique normal. Ce cas illustre la réussite de la prise en charge chirurgicale d’un abcès intracrânien d’origine otogène chez le chat et soutient le traitement chirurgical unilatéral guidé par les données cliniques et d’imagerie.Message clinique clé :Les abcès intracrâniens secondaires à une infection d’origine otogène doivent être envisagés chez les chats présentant des signes cliniques vestibulaires centraux et des crises d’épilepsie. Une approche chirurgicale combinée, associant craniotomie par trépanation et ostéotomie de la bulle tympanique ventrale, guidée par les données d’imagerie, peut aboutir à des résultats cliniques favorables.(Traduit par Dr Serge Messier).
Dengue virus and related flaviviruses are significant threats to global health, with no approved antiviral treatments available. Remdesivir triphosphate (RVn-TP) is a nucleotide analog that inhibits RNA-dependent RNA polymerases from many clinically important RNA viruses, including dengue virus. An orally bioavailable prodrug that efficiently delivers RVn-TP could facilitate early treatment for non-hospitalized dengue patients. To that end, we developed 1-O-octadecyl-2-O-benzyl-sn-glyceryl-P-remdesivir nucleoside (V2043, ODBG-P-RVn), a phospholipid prodrug that achieves RVn-TP delivery through improved oral bioavailability, potency, and pharmacokinetics. Here, we show that when compared to the parent compound remdesivir nucleoside (RVn), V2043 is a more potent in vitro inhibitor of multiple flaviviruses, including dengue, Zika, West Nile, and Japanese encephalitis viruses. In lethal prophylactic and therapeutic mouse models that recapitulate key aspects of severe dengue in humans, once-daily oral V2043 significantly decreased dengue serum viremia, clinical severity, weight loss, and mortality. Additionally, oral V2043 was well tolerated when administered daily for 14 days. These results demonstrate the potential therapeutic efficacy of V2043 to treat several clinically relevant flaviviruses, including dengue virus, the most prevalent and widespread arbovirus infection in the world.
To investigate the prevalence, onset, and contributing factors of oral mucosal lesions associated with orthodontic treatment. A comprehensive database search (PubMed, Scopus, Web of Science, Embase, Cochrane Library, and Google Scholar) was conducted according to PRISMA. Random-effects meta-analyses were conducted to estimate pooled prevalence and subgroup analyses of associations, where appropriate. A total of 18 studies met inclusion criteria, revealing a pooled prevalence of 58% for orthodontic appliance-associated oral lesions (95% CI: 50%-66%; I2 = 73.9%). Traumatic lesions showed significant variation by lesion type (p = 0.0093), with ulceration/erosion being the most prevalent. Allergic stomatitis and lichenoid reactions had a prevalence of 18% (95% CI: 13%-25%; I2 = 78%), while gingival overgrowth was at 54% (95% CI: 34%-73%; I2 = 96.8%). The strongest association with oral lesions was treatment duration (pooled effect estimate = 4.61; 95% CI: 3.15-6.75), followed by lifestyle and appliance-related factors. Findings should be interpreted cautiously. Oral mucosal lesions are commonly reported among patients undergoing orthodontic treatment, with considerable variability in lesion type, timing, and associated risk factors. These findings highlight the importance of preventive strategies, regular monitoring, and individualized patient management during orthodontic care. PROSPERO-CRD: 420251078164.
GNAO1-related disorders (GNAO1-RD), caused by variants in GNAO1 encoding the Gαo protein, comprise a broad phenotypic spectrum including movement disorders (MD) and/or epilepsy and are typically associated with developmental delay and intellectual disability. Currently, only symptomatic treatments are available. Zinc can restore guanosine triphosphate hydrolysis and cellular interactions of dysfunctional Gαo. ZINCGNAO1 evaluated the safety and feasibility of oral zinc supplementation in GNAO1-RD. ZINCGNAO1 was a 6-month, open-label, fixed-dose, single-centre pilot trial in Germany. Eligible participants were aged 6 months to 30 years, had a genetically confirmed GNAO1 variant, at least one hallmark feature of GNAO1-RD (MD, hypotonia, epilepsy, or global developmental delay), and had a Gross Motor Function Measure-66 (GMFM-66) score of 75 or lower. Zinc acetate dihydrate was administered orally in age-dependent dosages. Primary outcomes were safety, assessed by adverse event monitoring and laboratory analyses, and feasibility, defined as treatment adherence of at least 80% of days. Exploratory secondary outcomes included changes in MD severity (Burke-Fahn-Marsden Dystonia Rating Scale-Movement Score, BFMDRS-M, Abnormal involuntary movement scale, AIMS), and related disability (BFMDRS-Disability Score), motor function (GMFM-66), quality of life (Caregiver Priorities and Child Health Index of Life with Disabilities, CPCHILD), occupational performance (Canadian Occupational Performance Measure performance and satisfaction scores, COPM-P/-S), epilepsy, and participant- or caregiver-reported outcomes. This trial was registered at ClinicalTrials.gov (NCT06412653) and the EU Clinical Trials Register (2024-512735-72-00) and is complete. Between Aug 2, 2024, and Jan 27, 2025, 13 participants with 11 different genetic variants were enrolled; 11 completed the follow up of the trial. Mean age at inclusion was 8.0 years (range 0.5-25.1). Overall treatment feasibility was 84.6% (11/13). No treatment-related serious adverse events occurred, and laboratory monitoring did not identify clinically relevant safety concerns during the 6-month treatment period. Exploratory secondary outcomes showed no change in MD severity. The mean BFMDRS Disability Score decreased from 25.5 (SD 2.6) to 23.5 (SD 2.8; nominal p = 0.005). Mean GMFM-66 increased from 33.1 (SD 12.8) to 37.8 (SD 12.8, nominal p = 0.006). COPM-P increased from 2.6 (SD 0.8) to 3.8 (SD 1.3; nominal p = 0.003), and COPM-S from 2.7 (SD 0.9) to 4.1 (SD 1.7; nominal p = 0.002). CPCHILD and seizure occurrence showed no clear treatment-related change; two participants had seizures during the trial. Our preliminary findings show that oral zinc supplementation was safe and feasible in this GNAO1-RD population. Exploratory secondary outcomes suggested possible improvements in motor function and daily activities. Larger controlled trials are needed to assess efficacy. GNAO1-Gemeinsam nicht allein e.V.
Salivary gland dysfunction is a recognized complication of radioactive iodine (RAI) therapy for differentiated thyroid cancer. Oral sialagogues are commonly recommended, but their optimal timing remains uncertain. This systematic review compares early (<24 h) versus delayed (>24 h) sialagogue initiation. A literature search was conducted in Embase, PubMed, CINAHL, and Cochrane from inception to January 2026. "Early" protocols initiated stimulation within 24 h post-RAI, while "delayed" protocols initiated after 24 h. Methodological quality and risk of bias were assessed using Cochrane's ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions, 2016) tool. Three observational studies were included, comprising 818 adults with reported mean ages of 43-59 years. Interventions consisted primarily of lemon candy or oral vitamin C tablets. Primary outcomes included acute sialadenitis (pain and/or swelling), taste dysfunction, and xerostomia. Findings regarding acute salivary gland outcomes were inconsistent. Two earlier studies reported higher rates of acute sialadenitis with early stimulation (54.7-63.8% vs. 34.4-36.8%), taste dysfunction (37.5-39.0% vs. 18.8-25.6%), and xerostomia (23.8-46.9% vs. 11.2-29.7%) compared with delayed initiation. In contrast, the most recent propensity score-matched study, which evaluated a composite endpoint of acute salivary gland damage, reported lower event rates with early stimulation (4.78% vs. 15.22%). This review underscores how evidence regarding the optimal timing of sialagogue initiation after RAI remains inconsistent. These heterogeneous findings highlight the need for high-quality randomized controlled trials to establish evidence-based recommendations for sialagogue timing after RAI therapy.
Oral squamous cell carcinoma (OSSC) remains highly lethal, with resistance largely driven by cancer stem cells (CSCs). Mitochondrial reprogramming supports CSC redox control, self-renewal, and survival. This systematic review aimed to synthesize mitochondrial mechanisms sustaining CSCs in OSCC and evaluate their therapeutic relevance. Following PRISMA guidelines and a PROSPERO protocol (CRD420251088208), we searched major databases for studies investigating mitochondrial biogenesis, dynamics, mitophagy, or redox regulation in oral CSCs. Extracted data included molecular pathways, functional roles, and pharmacological targeting. Ten studies were eligible. Evidence shows that mitochondrial remodeling, through PGC-1α/ERRα-mediated biogenesis, DRP1-dependent fission, BNIP3/PINK1-regulated mitophagy, and NRF2-driven antioxidant signaling, supports metabolic flexibility and drug tolerance. These pathways activate stemness regulators, including EGFR/JNK/SOX2, YAP/CCN1, and SIRT1/PGC-1α, promoting adaptation and recurrence. Pharmacological interventions targeting these nodes, such as DRP1 inhibitors, SIRT1 or ERRα antagonists, and mitophagy-modulating agents (melatonin, verteporfin), showed potential to sensitize CSCs to conventional therapies. Mitochondria act as central regulators of CSC biology in OSCC and represent actionable therapeutic targets. Integrating mitochondrial dynamics, metabolism, and redox control provides a framework for overcoming resistance. Further preclinical and clinical studies are needed to translate these vulnerabilities into effective OSCC therapies. PROSPERO, CRD420251088208.
This paper systematically evaluated the efficacy, safety, and economic profile of oral Chinese patent medicine for the treatment of inflammatory bowel disease(IBD) through rapid health technology assessment. A total of 145 studies(including 110 RCTs) were included, involving 23 kinds of Chinese patent medicines. The results demonstrate that most Chinese patent medicines, used alone or combined with western medicine, exhibit superior outcomes in terms of total clinical efficacy, improvement of TCM syndrome patterns, and disease activity compared to western medicine alone, with a favorable safety. And the adverse reactions are predominantly mild gastrointestinal or neurological symptoms. Average daily costs range from 1.12 to 39.00 yuan. However, economic research is insufficient. There is sufficient evidence showing that Shenling Baizhu San/Pills/Granules and Bupi Yichang Wan for spleen deficiency with Qi stagnation, as well as Guchang Zhixie Wan/Capsules for liver depression with spleen deficiency pattern have notable advantages in efficacy, safety, and recurrence rate reduction. Nevertheless, the methodological quality of current research is generally low, with substantial heterogeneity in outcome indicators, and lack of long-term follow-up and real-world evidence. High-quality clinical research, pharmacoeconomic evaluations are urgently needed to support decision-making and rational drug use.
To address alveolar bone defects and the limitations of conventional grafts, tissue-engineered scaffolds have emerged as a promising alternative. Carboxymethyl chitosan (CMC) is a biocompatible and biodegradable polysaccharide with potential for bone regeneration; however, its brittleness and poor mechanical strength restrict its application. Here, we developed CMC-reduced graphene oxide (rGO) composite scaffolds with rGO concentrations of 0%, 0.5%, 1%, and 2% to overcome these drawbacks. The scaffolds were systematically characterized for their morphological, crystallographic, spectroscopic, and biomechanical properties, as well as their in vitro cytocompatibility and in vivo osteogenic performance. The incorporation of rGO enhanced structural homogeneity, optimized pore architecture, and significantly improved mechanical strength in a concentration-dependent manner, with tensile strength increasing from 1.64 to 8.13 MPa and elastic modulus from 1.14 to 25.05 MPa. In vitro, when MC3T3-E1 cells were grown in osteogenic medium, scaffolds loaded with 0.5%-1% rGO led to better cell survival and higher ALP activity-both pointing to stronger osteogenic differentiation. The 2% rGO scaffolds, however, turned out to be toxic to cells. Structural analyses confirmed the preservation of CMC crystallinity and revealed hydrogen bonding between rGO and CMC, elucidating the reinforcement mechanism. In a rat cranial defect model, the 1% rGO scaffold group demonstrated superior new bone formation, mineralization, and trabecular maturation. These findings underscore the dual function of rGO in simultaneously improving the mechanical integrity and osteogenic capacity of CMC-based scaffolds, with 0.5%-1% rGO identified as the optimal concentration window for bone tissue engineering applications.
Dental aesthetics plays a key role in children's social perception and psychosocial development. However, evidence on smile perception in children remains limited, highlighting the need for valid and reliable assessment tools. This study aimed to perform the cross-cultural adaptation and psychometric validation of the Smile Perception Questionnaire for Children Aged 8-10 Years (SPQ 8-10) for use in Turkish children. This observational methodological validity-reliability study included 300 healthy children aged 8-10 years who attended the Department of Pediatric Dentistry at Bursa Uludag University and met the predefined eligibility criteria. Eligible participants were healthy children aged 8-10 years whose parents provided informed consent; children with previous or ongoing orthodontic treatment, systemic diseases, or mental, physical, hearing, or visual impairments affecting communication or questionnaire completion were excluded. The SPQ (8-10) was translated into Turkish using forward-backward translation and expert review. Standardized perioral smile images were digitally generated to represent different dental conditions, and each participant evaluated one randomly assigned image using a five-point Likert scale. Exploratory factor analysis (principal axis factoring) and confirmatory factor analysis (DWLS estimation) were conducted to assess construct validity. Internal consistency (Cronbach's α, McDonald's ω) and test-retest reliability (ICC) were evaluated. Cronbach's α coefficient for the scale was 0.844, while McDonald's ω coefficient was 0.847. The analysis yielded ICC (3,1) = 0.803, 95% CI [0.628, 0.901], indicating that the scale had good temporal stability. CFI and TLI values above 0.95 and an SRMR value below 0.06 suggest a good fit. RMSEA value was at the threshold (0.084). The final 10-item Turkish version of the SPQ (8-10) demonstrates adequate psychometric properties in terms of factorial structure, internal consistency, and temporal stability.
Tinea capitis is still common in China. The gold standard for treatment is oral antifungal drugs. This study aimed to clarify the current epidemiological characteristics and efficacy of different treatments of tinea capitis in China. A multicenter, prospective real-world study involving 20 tertiary hospitals in China was conducted. From August 2020 to December 2021, 819 patients with tinea capitis were enrolled. Data concerning demography, clinical types, fungal tests, treatments and outcomes were analyzed. The most common pathogen was Microsporum canis (69.8%). Itraconazole (45.4%) and terbinafine (33.4%) were commonly used, while griseofulvin (16.0%) and fluconazole (5.3%) were less frequently prescribed. Most patients (81.9%) were clinically cured with the initial systemic antifungal treatment schemes. In treating gray patch tinea capitis, the success rate of oral terbinafine (58.1%) was significantly lower than itraconazole (92.2%) and fluconazole (91.3%). Treatment success rate of terbinafine for M. canis tinea capitis was 59.4%. All involved clinical centers are tertiary hospitals. Missing data may introduce bias. All four antifungal drugs have shown good efficacy and were well tolerated. More attention should be paid to the relatively low success rate of oral terbinafine in treating gray patch and M. canis tinea capitis.
Streptococcosis and motile Aeromonad septicemia (MAS) are major tilapia diseases causing significant economic losses. Feed-based vaccination offers a sustainable control strategy. However, the efficacy of oral vaccines in tilapia is largely constrained by inadequate adjuvant performance and associated side effects, while the safety, antigen interaction, and immunomodulatory potential of mycogenic metal oxide nanoparticles (MONPs) as a vaccine adjuvant remain insufficiently understood. This study evaluated the safety and immune responses of a novel feed-based bivalent vaccine (FBBV) containing formalin-killed Streptococcus agalactiae and Aeromonas hydrophila, enriched with mycogenic zinc oxide (ZnO-NPs) or aluminium oxide nanoparticles (Al2O3-NPs), in red hybrid tilapia. Four hundred and eighty red hybrid tilapia (10.0 ± 1.5 g) were randomly assigned to four groups (control, AquaBooster, FBBV/ZnO-NPs, and FBBV/Al2O3-NPs) and orally immunized at weeks 0, 2, and 6. Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) analyses suggested interactions between mycogenic MONPs and formalin-killed whole cells (FKWC). Furthermore, spray-coating onto feed maintained the estimated DNA abundance of formalin-killed S. agalactiae while reducing that of A. hydrophila by approximately three-fold. Haematological parameters were largely stable, though white blood cell (WBC) and lymphocytes increased in all vaccinated groups. Histopathological examination revealed generally mild alterations in the control, AquaBooster, and FBBV/Al2O3-NPs groups, whereas the FBBV/ZnO-NP group exhibited marked renal mineralization. Meanwhile, spleen histology was comparable across groups. Moreover, early IgM induction occurred in FBBV/ZnO-NPs, while sustained IgM levels were seen in FBBV/Al2O3-NPs and AquaBooster groups. Gut-associated lymphoid tissue (GALT) area was significantly increased in all vaccinated groups compared with the control. Hindgut qPCR demonstrated comparable estimated DNA abundance of FKWC among the vaccinated groups, whereas hindgut RT-qPCR analysis revealed upregulation of innate (IL-1β, TNF-α) and adaptive (IgM, IgT) immune markers. Overall, both MONP formulations stimulated immune responses; however, their safety profiles differed. The Al2O3-NPs formulation exhibited minimal histopathological alterations, whereas the ZnO-NP formulation induced notable renal mineralization, indicating that this formulation warrants further dose optimization and safety evaluation.
The annual economic burden of obesity has reached 190 billion dollars in the US and around 62 billion Egyptian pounds in Egypt. It is linked to many harmful diseases, including diabetes mellitus, cardiovascular, liver, reproductive, bone diseases, and many others. Modeling of obesity and obesity-associated comorbidities represents a fruitful area of research. Animal models of obesity have many limitations regarding reliability, translatability, and extrapolation to human obesity. Microfluidic "organ on a chip" has emerged in recent decades as a potent in vitro tool for studying human diseases, offering advantages over traditional in vitro models, thereby facilitating the development of a human on a chip model. This review will briefly discuss obesity-associated metabolic disturbances and the recent publications that tried to use microfluidic devices to answer obesity-related questions. This review covers the role of in vitro modeling using microfluidic devices in obesity research. The different species of invertebrates utilized in obesity research have also been investigated, including nematodes, with a highlight on Caenorhabditis elegans. Research on anti-obesity drugs, which could potentially aid in managing obesity, has been increasing daily. Natural anti-obesity phytoconstituents have shown considerable therapeutic potential in obesity, with many plant extracts and single components with promising effects. In conclusion, integrating microfluidics, invertebrate models, and phytochemical screening is promising for obesity research, yet it requires further standardisation and clinical validation to enable personalised therapies.
Pongamia pinnata (L.) Pierre, a medicinal plant traditionally used in Indian ethnomedicine, was evaluated for its antidiarrheal, antibacterial, and antioxidant properties through a combination of in vitro, in vivo, and in silico approaches. This study aims to study the traditional use of plants in medicine and identify a suitable secondary metabolite that can help reduce bacterial growth in living systems, thereby lowering the risk of waterborne diseases and diarrhea. Screening of P. pinnata leaf extract confirmed the presence of various bioactive classes, including alkaloids, flavonoids, etc., and that it also had strong antioxidant activity. In vitro antibacterial assays revealed that the plant extract effectively inhibited multiple waterborne pathogens, particularly Shigella dysenteriae Castellani and Chalmers, 1919, and in vivo studies also showed significant dose-dependent antidiarrheal effects. Acute oral toxicity tests at high doses confirmed the extract's safety, with no adverse effects on body weight, behavior, or vital organs. GC-MS analysis revealed various secondary metabolites with N-decanoic acid as the most abundant in the plant extract. Notably, 1,2,5,6-di-O-isopropylidene-3-O-methanesulfonyl glucofuranose and spiro{2,4}heptane derivatives exhibited stronger binding affinities than the standard drug ampicillin in molecular docking studies with penicillin-binding proteins (PBPs). These findings suggest that P. pinnata harbors potent metabolites with significant antidiarrheal and antibacterial activity, offering promise for the development of plant-based therapeutics against waterborne bacterial pathogens. The integration of experimental and computational approaches strengthens its candidacy for future drug development targeting diarrheal diseases.
This review aims to summarize current evidence on the interactions among bacteria, fungi, and bacteriophages in periodontitis and peri-implantitis, and to discuss their ecological significance, pathogenic mechanisms, and potential clinical implications. This review synthesizes current insights into the roles of the oral microbiome in these diseases, with a focus on the critical interplay between bacteria, fungi, and bacteriophages. Our analysis demonstrates that disease progression is marked by a shift toward polymicrobial synergy. Keystone pathogens and opportunistic fungi engage in intricate interactions within biofilms, including physical coadhesion and metabolic cross-feeding, which enhance microbial resilience and virulence. Bacteriophages, acting as natural modulators of bacterial populations, emerge as a promising therapeutic approach to disrupt these pathogenic communities. This bacteria-fungi-phage consortium synergistically modulates host immune responses, fostering chronic inflammation and tissue destruction. An integrated, multikingdom perspective on the oral ecosystem is critical for clinical advancement. Future strategies should prioritize personalized interventions that combine multiomics biomarker analysis with targeted therapies to effectively disrupt polymicrobial biofilms, restore homeostasis, and overcome antimicrobial resistance.
Introduction Diabetes is among the many known chronic diseases resulting from the inability of the body to produce insulin. The use of traditional drugs such as sulfonylurea, biguanide, and thiazolidinediones has been associated with some side effects, hence making researchers turn their attention toward herbal medicine as a treatment or prevention option for diabetes. Hence, the present study was designed to evaluate and compare the metabolic effects of allantoin (5 mg/kg and 10 mg/kg), metformin (500 mg/kg), and their combination on blood glucose and body weight in low-dose streptozotocin (STZ)-induced diabetic Wistar rats. Methods An in vivo study employed a randomized, controlled, parallel-group, preclinical experimental design consisting of a total of 36 young adult (8-10 weeks old) male Wistar rats (Rattus norvegicus) weighing 200-260 g, which were randomly assigned to six experimental groups, namely, G1 to G6. G1 and G2 served as non-diabetic and diabetic controls administered intraperitoneally (ip) with 2 ml of normal saline (NS) and STZ 45 mg/kg + 2 ml NS, respectively. G3, G4, G5, and G6 groups served as treatment groups and received STZ 45 mg/kg, concurrently administered intraperitoneally with allantoin (ALN) 5 mg/kg, ALN 10 mg/kg, metformin (MET) 500 mg/kg (oral), and ALN 5 mg/kg (ip) + MET 500 mg/kg (oral), respectively. Fasting blood sugar (FBS) estimation was done for nine days daily after STZ injection, after diagnosis of diabetes mellitus on the 9th/10th day, and on the 28th day of treatment. Body weight of experimental animals was recorded once weekly on days 0, 7, 14, 21, and 28. Results FBS levels differed significantly among groups at baseline and day 28 (p < 0.0001). Diabetic controls maintained persistently elevated glucose levels, whereas ALN treatment at 5 mg/kg (301.17 ± 11.18 vs. 218.33 ± 10.11; -82.84; p < 0.001) and ALN 10 mg/kg (302.83 ± 5.08 vs. 171.17 ± 7.88; -131.66; p < 0.001) significantly reduced FBS in a dose-dependent manner. Metformin monotherapy markedly improved glycemic control (297.00 ± 17.73 vs. 126.00 ± 10.10; -171.00; p < 0.001), while combination therapy with ALN and metformin produced the greatest reduction in glucose levels (302.50 ± 11.41 vs. 120.00 ± 9.57; -182.50; p < 0.001), suggesting additive antihyperglycemic effects. ALN 10 mg/kg significantly increased body weight (p = 0.002). Conclusion Allantoin, particularly along with metformin, offers promising therapeutic potential for the management of diabetes and associated metabolic alterations.
This study investigated the mechanism by which Xiaoyao San ameliorates "brain-gut" interaction disorders in chronic stress-induced mice by examining its effects on T helper 1 cell(Th1)/T helper 2 cell(Th2) immune balance. Forty male C57BL/6 mice(6-8 weeks old, SPF grade) were randomly assigned to four groups(n=10 per group): control group, model group, Xiaoyao San group(7.63 g·kg~(-1)), and fluoxetine hydrochloride group(4.11 mg·kg~(-1)). Except for the control group, all groups underwent 28 days of chronic unpredictable mild stress(CUMS) to establish the model. Behavioral tests were conducted on day 28. From day 29, the Xiaoyao San and fluoxetine hydrochloride groups received corresponding drug solutions via oral gavage for 28 days(once daily), while the control and model groups received equivalent volumes of saline. CUMS modeling continued uninterrupted during the administration period. Behavioral assessments were repeated on day 56, with body weight monitored throughout the experiment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in intestinal tissues. The villus height and crypt depth were measured, and their ratio was calculated. Immunohistochemistry(IHC) was employed to detect the expression of tight junction proteins zonula occludens-1(ZO-1) and occludin in the intestinal mucosa. Serum levels of interferon-γ(IFN-γ), interleukin(IL)-2, IL-4, IL-10, corticosterone(CORT), gastrin(GAS), motilin(MTL), and somatostatin(SS) were measured using enzyme-linked immunosorbent assay(ELISA) and subjected to correlation analysis. Western blot was performed to assess T-box transcription factor T-bet and GATA-binding protein 3(GATA-3) protein expression in the hypothalamus and intestinal tissues. The results demonstrated that Xiaoyao San significantly alleviated CUMS-induced depressive-like behaviors, including weight loss, reduced sucrose preference, and decreased locomotor activity in the open field test. HE staining indicated that Xiaoyao San effectively restored intestinal villus structure and increased the villus height-to-crypt depth ratio. IHC results showed that Xiaoyao San enhanced the expression of occludin and ZO-1 related to intestinal mucosal barrier, suggesting improved intestinal barrier function. ELISA analysis revealed that Xiaoyao San significantly decreased serum levels of CORT, SS, IFN-γ, and IL-2, while increasing GAS, MTL, IL-4, and IL-10, indicating mitigation of stress-induced damage and inflammatory responses, as well as regulation of brain-gut peptide secretion. Western blot results showed that Xiaoyao San significantly reduced T-bet protein expression and the T-bet/GATA-3 ratio in both the hypothalamus and intestinal tissues, suggesting correction of Th1/Th2 immune imbalance induced by CUMS. Correlation analysis indicated significant associations between brain-gut peptides and Th1/Th2-related inflammatory factors, implying a link between Th1/Th2 inflammatory responses and brain-gut regulatory function. In conclusion, Xiaoyao San ameliorates brain-gut interaction disorders in chronic stress mice, potentially through restoring Th1/Th2 immune balance, attenuating inflammatory responses, and modulating "brain-gut" peptide secretion.