Temporomandibular joint osteoarthritis is a degenerative condition characterized by cartilage loss and structural joint alterations. Experimental evidence suggests that exosome-based therapies may influence joint repair processes. This study evaluated the effects of surgical debridement, exosome therapy, and their combination on structural and histologic outcomes in an experimental temporomandibular joint osteoarthritis model. Twenty-eight Wistar albino rats were randomly assigned to 4 groups: control, exosome, surgery, and surgery plus exosome. Osteoarthritis was chemically induced in all animals. Exosomes were administered by intra-articular injection, and surgical groups underwent standardized debridement. After a 5-week follow-up period, mandibular condyles were evaluated using microcomputed tomography and histopathologic analysis based on the Mankin scoring system. The combination therapy group demonstrated the highest bone volume to total volume ratio compared with the other groups (P<0.05). Trabecular number was significantly higher in the exosome group than in controls (P<0.05). Histologically, Mankin scores were lowest in the combination group and highest in controls (P<0.001), whereas differences between the combination and exosome groups were not statistically significant. Overall, combined surgical and exosome-based treatment was associated with improvements in selected structural and histologic parameters, whereas other outcomes were comparable among treatment groups.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infects the gastrointestinal tract; however, its effects on the stomach and underlying mechanisms remain unknown. The presence of ACE2 (angiotensin-converting enzyme 2) receptors in the gastric mucosa suggests that the stomach is vulnerable to infection. This study is the first to examine SARS-CoV-2’s impact on distinct cell types within gastric tissue, alongside the involvement of protective mechanisms and cell death pathways. K18-hACE2 transgenic mice (n = 20) were divided into control and SARS-CoV-2 groups, and their gastric tissues were analyzed on day 8 post-infection to represent the acute phase. Epithelial degeneration, hemorrhage, glandular cell damage, inflammatory infiltration, and muscle injury were assessed and scored, alongside apoptosis, pyroptosis, necroptosis, and Galectin-3 expression levels. Ultrastructural changes were identified using transmission electron microscopy. The SARS-CoV-2 group exhibited significant epithelial desquamation, extensive tissue damage (P < 0.0001), diminished mucin content, elevated apoptosis (P = 0.0279) and pyroptosis (P = 0.0265), and reduced Galectin-3 expression (P = 0.0211). Parietal cells showed pronounced structural damage and strong SARS-CoV-2 positivity, highlighting their susceptibility and potential role in gastric dysfunction during infection. Virus-like particles (70–110 nm) were observed within cells and in vesicles. Enteroendocrine cells displayed heightened activity. SARS-CoV-2 infection caused significant damage to gastric epithelial and parietal cells through inflammatory, apoptotic, and pyroptotic mechanisms, likely exacerbated by reduced Galectin-3 expression and consequent impairment of gastric protection. This damage may amplify susceptibility to secondary infections, such as H. pylori, and could contribute to clinical symptoms such as nausea, dyspepsia, and unexplained gastric complaints observed in SARS-CoV-2 cases.

The anti-inflammatory effect of the ethanol extract of Momordica charantia in two different chemically induced inflammatory bowel disease models, which are frequently used in experimental studies, was investigated. For this purpose, IBD models were created with acetic acid (AA) and 2,4,6 trinitrobenzene sulphonic acid (TNBS) in rats and 300 mg/kg M.charantia extract was given by oral gavage for 10 days. In the animal experiment phase, a total of 42 animals in six groups were arranged so that two different experimental models could be studied simultaneously. Colon tissues were examined at light and electron microscopy levels. In the microscopic examination, areas of inflammation extending to the muscularis externa were observed in the macroscopically severely damaged areas in both IBD model groups, and epithelial damage, mucosal inflammation, and crypt abscess were observed in the macroscopically less damaged areas. Microscopic large intestine damage was significantly reduced in M.charantia administered groups compared to disease models. TNF-α and IL-1β expression, which was determined to be increased in the AA and TNBS groups immunohistochemically, was observed to decrease in the treatment groups. The surface epithelium was evaluated by electron microscopic observations. This study demonstrates the positive effect of M.charantia ethanol extract on colon histopathology in two different IBD models and highlights the importance of considering inflammation-related cell populations in the treatment of this disease.

Multifunctional hydrogel wound dressing with high hemostatic, antioxidant, and self-healing activity is desirable in clinical applications. In this contribution, we developed two distinct hydrogel formulations, namely PZ and PTBA, by employing low methoxyl pectin (P), zeolite, or 2-thiobarbituric acid (TBA) for sustained release of procaine (PC) in a controlled manner up to 40 h. These hydrogel systems (PZ and PTBA) utilize dynamic reversible hydrogen bonds between the components and a metal coordination bond between carboxyl acid groups of pectin chains and Ca2+ to confer self-healing properties, as demonstrated by molecular dynamics (MD) and rheological analyses. Moreover, PZ and PTBA hydrogels possess superior antioxidant, hemostasis, biocompatibility, and antibacterial activities. The data from the mouse skin incision model and infected full-thickness skin wound model demonstrated the highest wound closure rate (wound closure area per day) was achieved by the PZ (4.72) and PTBA (4.62) groups on day 21, which was better than the control (4.2) and Kaltostat groups (4.05) (p < 0.05). PZ and PTBA's effectiveness in wound closure and acceleration of the wound healing process, highlighting its significant potential in wound management.

An ideal aesthetic restorative material should be attached to the tooth tissues by adhesion, have a smooth surface as possible, should not cause toxic reactions in the pulp and discoloration and microleakage. This study aims at comparatively assess the cytotoxicity of current adhesive systems on human dental pulp cells. The adequate density of human pulp cells was observed from the ready cell line. The passaging was performed and the 3rd passage cells were selected. Adhesive systems and MTA were used on the cultures. Trypan blue staining was conducted on the cells at the 1st, 2nd, 3rd days and a count of live and dead cells using a light microscope. The dead cells whose membrane integrity was impaired by staining with trypan blue and the viability rate was determined using live and dead cell numbers. Data analysis was performed using IBM SPSS Statistics 22. A significant difference in vialibity rates between adhesive systems was observed on the first day. No significant statistical differences were observed on the 2nd and 3rd days (p < 0.05). Futurabond M showed similar biocompatibility with MTA on human pulp cells and it can be applied in cavities with 1–1.5 mm hard tissue between pulp and dentine.

Background and Objectives: Lymphedema is a progressive, chronic condition. Traumatic damage to the lymphatics, removal of lymph nodes, and/or radiation are the major causes of fibrosis and a subsequent pathological cascade. Macrophages play a crucial role in wound healing, with M1 macrophages known for their pro-inflammatory effects and M2 macrophages recognized for their anti-inflammatory effects, including improved angiogenesis, lymph angiogenesis, and tissue healing. This study aims to assess the use of calcitriol to alter the M2/M1 macrophage balance, reduce tissue fibrosis in a lymphedema model, promote new micro-lymphatic vessel formation, and evaluate the benefits of active vitamin D. Material and Methods: Forty-five rats were randomly divided into three groups: control surgery (group A), surgery with preoperative–postoperative calcitriol (group B), and postoperative calcitriol (group C). One week after the surgical ablation a total dose of 20 Gy radiation therapy was administered to the operated groin region. Micro-computed tomography was used for limb volume calculation, fluorescence lymphatic imaging was used to assess the presence of lymphedema, and histopathological analyses were conducted to evaluate the M1/M2 macrophage ratio, fibrosis accumulation, and lymph angiogenesis. Results: The micro-computed tomography evaluation revealed that 75% of the rats of group A exhibited long-lasting lymphedema. In group B, the initial lymphedema ratio was the lowest, affecting only 25% of the rats. After ligating the main vessels, a linear lymphatic microvascular structure was observed in groups B and C. Group B had a significant increase in M2 macrophages and newly formed lymphatic vessels (p < 0.05). However, group A showed a significant elevation of M1 macrophages and collagen accumulation (p < 0.05) in the surgically treated hind limb. Conclusions: Both histological analyses and clinical results reported a relevant influence of calcitriol administration. Among all groups, the most favorable outcomes were seen in group B (prophylaxis group). Hence, calcitriol administration could play a crucial role in enhancing the migration of M2 macrophages to the damaged tissue. Such migration may contribute to lymphedema resolution either by enhancing the organization of superficial lymphatic vessels or resolving fibrosis, or with a combination of both these mechanisms.

Objective: Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disease. Besides amyloid beta (A(3) and tau accumulations, inflammation also contributes to AD pathogenesis. NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in microglia is thought to be associated with AD. Since animal models of AD do not accurately reflect human pathology, in our study, human induced pluripotent stem cells (iPSCs) were differentiated into microglia, and their potential to be used in NLRP3 pathway-related mechanisms in AD was investigated. Material and Method: iPSC cell lines of AD, isogenic, or control genotypes were differentiated into microglia and cells from different stages of the differentiation were characterized by flow cytometry, real-time quantitative polymerase chain reaction (RTqPCR), immunocytochemistry, and Western blot. The expression of proteins associated with the NLRP3 pathway was investigated by Western blot. For functional analysis, cytokine release was assessed by Enzyme-linked immunosorbent assay (ELISA) upon NLRP3 inflammasome activators (lipopolysaccharide (LPS), A13) and inhibitor (cytokine release inhibitory drug 3, CRID3) treatments. The phagocytosis of pHrodo particles and A13 were evaluated by flow cytometry, fluorescence microscopy, and live cell imaging system. Result: In our study, we could differentiate microglia from iPSCs derived from different genotypes. These microglia cells expressed various microglia and NLRP3 inflammasome-related markers and were able to phagocytose pHrodo particles and A13. The stimulation of the microglia cells with LPS and A13 caused IL1beta and IL-18 release, while CRID3 reversed this effect. Conclusion: Our results show that iPSC-derived microglia generated in this study recapitulate microglia functional characteristics and can therefore be used to study NLRP3 pathway-associated disease mechanisms and treatment options.

The 3-methyl-4-nitrophenol (PNMC), found in pesticides and diesel exhaust particles (DEP), increases oxidative stress and induces tissue injury, while Noni ( Morinda citrifolia L ) is known for its antioxidant and anti-apoptotic properties. This study aimed to investigate the potential benefits of Noni juice on PNMCinduced nephrotoxicity in rats. A total of 56 adult male Sprague-Dawley rats were randomly divided into eight groups (n=7 each). These groups included: Control (PBS+0.05% Tween 80 S/C), Noni (2 ml Noni juice per rat), 1 mg/kg PNMC, 10 mg/kg PNMC, 100 mg/kg PNMC, Noni+1 mg/kg PNMC, Noni+10 mg/kg PNMC and Noni+100 mg/kg PNMC. Noni juice was given @ 2ml per rat through oral gavage, while PNMC was given through S/C injections. Treatments were given daily for five days. Then the rats were euthanized and blood samples were collected for serum biochemical analysis and assessing oxidative stress status. Kidneys were processed for histopathological and ultrastructural analyses and immunohistochemical demonstration of iNOS, eNOS, NGAL, active caspase-3 expressions and apoptotic index. The iNOS protein level was also assessed by ELISA. Results showed dose-dependent increasing degenerative changes in the kidneys with 1, 10 and 100 mg/kg of PNMC. The severity of these lesions was reduced in Noni+PNMC treatment groups. Mitochondrial damage occurred with 100mg/kg PNMC. A significant dose-dependent increase was recorded in iNOS, eNOS, NGAL and active caspase-3 expressions and apoptotic index in the kidneys with PNMC, while these parameters were decreased with Noni juice administration. Oxidative stress was highest with 100 mg/kg PNMC and decreased in Noni+PNMC groups. In conclusion, Noni juice efficiently attenuated PNMC-induced acute renal toxicity; however, its efficacy against PNMC induced chronic toxic effects need to be investigated.

Under inflammatory conditions, macrophage dominance affects the degree of inflammation. We assessed the effects of the active vitamin D (calcitriol) administration on inflammatory processes and macrophage dominance and aimed to determine the potential positive macroscopic and histological effects in supermicrosurgical arterial anastomosis model of rats. Forty rats were divided into five groups: control surgery (Group 1), surgery with preoperative (Group 2), post-operative (Group 3), perioperative (Group 4) systemic calcitriol and surgery with local calcitriol (Group 5). Eighty femoral artery anastomoses were planned in both legs of rats. Systemic calcitriol was administered intraperitoneally daily to the animals in the relevant groups. Preoperative vessel diameter measurements were taken before anastomosis. Three weeks post-surgery, post-operative vessel diameter measurements were taken, anastomosis patency was assessed and vascular segments were collected for histological examination, which included assessment of M1 and M2 macrophage depolarisation, leucocyte infiltration, intima-media ratio and luminal gap scoring. Systemic calcitriol administration (pre-, post- or perioperative) significantly improved the vessel diameter (p < 0.001); there was no significant difference among Groups 2-4. Histological findings revealed that Groups 3 and 4 had lower intima-media ratios (p < 0.05 and p < 0.01), higher M2-M1 macrophage ratios (p < 0.01 and p < 0.001) and lower leucocyte infiltration (p < 0.05, p < 0.01 and p < 0.001). Local calcitriol administration had no vasodilatory effects or resulted in positive histological outcomes. Although the administration of calcitriol preand post-operatively increased the vessel diameter, the latter appeared to have a more favourable impact on the histological analyses. (c) 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Amaç: Ratlarda, deneysel monooküler deprivasyon ambliyopisi modelinde rolipramın, vizüel kortikal plastisite üzerindeki etkisinin elektrofizyolojik ve elektron mikroskobik olarak incelenmesidir. Gereç ve Yöntemler: Yirmi dört Wistar albino cinsi rat, her grupta 4 rat olacak şekilde rastgele 6 gruba ayrıldı. Kontrol grubu dışındaki ratlar dışında tüm ratların sağ göz kapakları 21-45. günleri arası sütüre edilerek monooküler deprivasyon modeli oluşturuldu. Kırk altıncı günde tüm ratlara 10 gün boyunca rolipram veya rolipramı çözmek için kullandığımız sıvı uygulandı. Sinaptik kavşaktaki ultrastrüktürel modifikasyonlar ve görsel uyarılmış potansiyellerdeki (VEP) değişiklikler analiz edildi. Bulgular: Deprivasyon ambliyopisi modelinde VEP'te P2 latansının uzadığı, amplütüdün azaldığı ve rolipram ile tedavi sonrası ise latansın kısaldığı ve amplitüdün arttığı ve kontrol grubuna yaklaştığı görüldü. Deprivasyon ambliyopisi modelinde piramidal nöronlardaki sinapsların ultrastrüktüral yapısının bozulduğu, sinaptik yarığın genişlediği, sinaptik aktif zonun uzunluğunun kısaldığı, postsinaptik dansite kalınlığının azaldığı ve rolipram ile tedavi sonrası ise bu değerlerin kontrol grubuna yaklaştığı görüldü. Sonuç: Bu çalışma, rolipramın ratlardaki ambliyopi modelinde, vizüel kortekste yapısal ve fonksiyonel iyileşmeyi sağladığını göstermektedir. Rolipram, ambliyopi tedavisinde umut vadetmektedir ve ileri araştırmalara gerek vardır.

We performed dual immunohistochemistry for CD163/CD34 and CD68/CD34 in 108 renal transplant indication biopsies to investigate the presence and distribution of macrophages in various renal compartments. All Banff scores and diagnoses were revised according to the Banff 2019 classification. CD163 and CD68 positive cell counts (CD163pos and CD68pos) were evaluated in the interstitium, glomerular mesangium, and, within glomerular and peritubular capillaries. The diagnosis was antibody-mediated rejection (ABMR) in 38 (35.2%), T-cell mediated rejection (TCMR) in 24 (22.2%), mixed rejection in 30 (27.8%), and no rejection in 16 (14.8%). Banff lesion scores t, i, and ti were correlated with both CD163 and CD68 interstitial inflammation scores (r > 0.30; P < 0.05). Glomerular total CD163pos was correlated to Banff lesion scores g and cg (r > 0.30; P < 0.05). Glomerular total, mesangial, and intracapillary CD68pos were correlated with g (r > 0.30; P < 0.05). Both glomerular total and peritubular capillary CD68pos were correlated with peritubular capillaritis (r > 0.30; P < 0.05). Glomerular CD163pos were significantly higher in ABMR compared with no rejection, in mixed rejection compared with no rejection and TCMR. CD163pos in peritubular capillaries was significantly higher in mixed rejection compared with no rejection. Glomerular CD68pos was significantly higher in ABMR compared with no rejection. CD68pos per peritubular capillary was higher in mixed rejection, ABMR, and TCMR compared with no rejection. In conclusion, compared with CD68 positive macrophages, localization of CD163 positive macrophages in various renal compartments seems to be different among rejection subtypes and their glomerular infiltration seems to be more specific for the presence of ABMR component.

Objective: This study investigated the potential synergistic effects of propolis, an antitumor and antioxidant natural product, and carboplatin, a frequently used chemotherapeutic agent for endometrial adenocarcinoma, one of the most common gynaecological cancers treatment. Materials and Methods: Ishikawa endometrial adenocarcinoma and healthy fibroblast (3T3) cell lines were treated with 0.5 mu L of carboplatin and 5 mu L of propolis. Cell count, viability, migration, ultrastructure, apoptosis, and cell cycle changes were assessed using cytological and immunocytochemical methods, flow cytometry, and transmission electron microscopy (TEM). Results: Propolis and carboplatin exhibited cytotoxic effects on Ishikawa cells. The combination of the two agents further reduced cell viability and migration. Propolis induced apoptosis through the intrinsic pathway and arrested the cell cycle in the G1 phase. TEM analysis revealed apoptosis in Ishikawa cells treated with propolis or carboplatin, while the carboplatin+propolis combination resulted in severe cell budding, apoptosis, and vacuolization. Migrasome-like structures were only observed in the Ishikawa carboplatin group. Minimal effects were observed on 3T3 cells. Conclusion: Propolis demonstrated cytotoxic, anti-proliferative, and proapoptotic effects on tumor cells without harming healthy cells. Its ability to prevent migrasome formation suggests it may reduce chemotherapeutic resistance. Therefore, propolis shows promise as a potential enhancer of anticancer treatments.

Background: Although most patients with atypical hemolytic uremic syndrome (aHUS) have variants in genes participating in alternative complement pathways, rare variants in non-complement pathway-related genes, including DGKE, INF2, MMACHC, PLG, and THBD, have also been described. Case Presentation: We report an 18-year-old male patient with renal biopsy-proven chronic thrombotic microangiopathy that raised suspicion of aHUS. Whole-exome sequencing revealed a novel pathogenic homozygous MMACHC c.484G>T (p.Gly162Trp) variant. Subsequently, clinical and laboratory findings confirmed cobalamin C (Cbl C) deficiency. Also, homozygous missense c.1112C>T PLG (p.Thr371Ile) variant was detected (it had been reported as a variant of unknown significance). However, the low serum plasminogen (PLG) activity proved the pathogenicity of c.1112C>T. Hence, the patient was diagnosed with concurrent Cbl C and PLG deficiencies. Segregation analysis revealed that the mother and father had the same heterozygous PLG and MMACHC variants. PLG variants have generally been described in aHUS patients concomitant with complement gene variants in the literature; therefore, the association between aHUS and PLG variants is controversial. The possible contribution of PLG deficiency to thrombotic microangiopathy was also discussed in this case. Conclusion: Non-complement-mediated aHUS is an exceptional disorder. A limited number of genes are involved in this entity. To our knowledge, this is the first aHUS patient diagnosed with both Cbl C and PLG deficiencies in the literature.

BACKGROUND: In brachial plexus birth palsy (BPBP), botulinum toxin may be utilized to prevent glenohumeral dysplasia and to maintain the stable growth of the glenohumeral joint. Repeated injections may cause muscular atrophy and their functional effects are uncertain. The aim of this study was to compare the microstructure and the function of the muscles that received two injections before transfer with the muscles that were not injected. METHODS: BPBP patients that were operated between January 2013 and December 2015 were included in the study. Latissimus dorsi and teres major muscles were transferred to humerus in standard fashion. Patients were divided in two groups according to bo-tulinum toxin status. Group 1 was toxin negative whereas Group 2 was toxin positive. For each patient, mean latissimus dorsi myocyte thickness (LDMT) was measured with electron microscopy and pre-operative and post-operative active shoulder abduction, flexion, external and internal rotation, and Mallet scores were evaluated with goniometry. RESULTS: Fourteen patients (seven patients per group) were evaluated. Five patients were female whereas nine were male. Mean LDMT was not affected significantly (p>0.05). The operation improved shoulder abduction, flexion, and external rotation significantly (p<0.05), independent of the toxin status. The internal rotation decreased significantly only in Group 2 (p<0.05). The Mallet score increased in both groups, but it was not significant (p>0.05), independent of the toxin status. CONCLUSION: Botulinum toxin that was applied twice prevented glenohumeral dysplasia and it did not cause permanent latissimus dorsi muscle atropy and function loss in late period. It augmented upper extremity functions by alleviating internal rotation contracture.

Vitiligo is a depigmentation disease which affects skin and hair follicles with a prevalence of 0.5%-1% worldwide. In this study, we aimed to investigate treatmental potential of dermis-derived cells in monobenzone (MBEH)-induced mouse vitiligo model with light and electron microscopy. MBEH (40%) cream was topically applied to C57BL/6 mice until depigmentation occured in vitiligo and experimental groups. In experimental groups, dermis-derived cells obtained from back skin biopsy samples before induction of vitiligo, were injected intradermally to vitiligo mice. On Days 3 and 15 after cell transplantation to experimental groups, skin biopsies were compared with biopsies of control and vitiligo groups. Dermis-derived cells obtained from back skin biopsy samples of experimental groups showed nestin and versican immunoreactivity. Melanin in hair follicles of control group was detected by histochemical stainings (Haematoxylin and eosin and Fontana-Masson) whereas sparse melanin granules were observed in hair follicles of vitiligo group. In experimental groups, there was an increase in the number of hair follicles with melanin compared with vitiligo group. We observed MART-1 immunoreactive cells mostly around the hair follicles in control group and within dermis in vitiligo group. Electron microscopic investigation showed presence of melanosomes in hair follicles of control group and lacking in vitiligo group. In experimental groups, both type of hair follicles were observed with electron microscope. Our data suggest that autologously transplanted dermis-derived cells may be effective in vitiligo treatment by contrubuting to melanin production.