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AIMS: Acute kidney injury (AKI) is a life-threatening condition marked by sudden kidney function loss and azotemia. While its management is limited to supportive care, the effects of hyperbaric oxygen therapy (HBO) on AKI remain a subject of conflicting animal research. This study aimed to systematically review and meta-analyze HBO's effects on renal function biomarkers serum creatinine (SCr) and blood urea nitrogen (BUN) in murine AKI models, also exploring tissue-level nephroprotection. MAIN METHODS: The PUBMED, SciELO, and LILACS databases were searched until September 5, 2024. Effect sizes of HBO on SCr and BUN levels were expressed as standardized mean difference (SMD) alongside 95 % confidence interval (CI), calculated by random-effects model. Extracted data also included murine specie/strain, HBO parameters, AKI induction method (toxic, ischemic, others), and histological findings. Study quality and publication bias were respectively assessed using the CAMARADES checklist and Egger's test. This review adhered to PRISMA guidelines and was registered in PROSPERO (CRD42022369804). KEY FINDINGS: Data synthesis from 21 studies demonstrates that HBO effectively reduces azotemia in AKI-affected animals (SCr's SMD = -1.69, 95 % CI = -2.38 to -0.99, P < 0.001; BUN's SMD = -1.51, 95 % CI = -2.32 to -0.71, P < 0.001) while mitigating histological damage. Subgroup analyses indicate that HBO particularly benefits ischemic and other AKI types (P < 0.05). In contrast, data from toxic AKI models were inconclusive due to insufficient statistical power (P > 0.05, 1-ß < 30 %). SIGNIFICANCE: This meta-analysis provides compelling evidence supporting the adjunctive use of HBO in AKI management.

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Bispectral index with density spectral array (BIS-DSA) monitoring during hyperbaric oxygen therapy of a case with inner ear and cerebral decompression sickness is described. During the initial treatment, a particular DSA pattern was found, which resolved after four treatments. Clinical resolution of the symptoms accompanied this improvement. The particular BIS-DSA pattern described in this case is concordant with a potential hypo-perfusion of the cortex related to decompression stress. This case suggests that BIS-DSA monitoring may be an easy, cost-effective, and viable form of neuro-monitoring during hyperbaric oxygen treatment for decompression sickness.

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Mild hyperbaric oxygen therapy (mHBOT) is an adjuvant therapy used in conditions where tissue oxygenation is reduced and is implemented using pressures less than 1.5 ATA and 100% O2 (instead of the classical HBOT at 1.9-3 ATA) which results in cheaper, easier to implement, and equally effective. mHBOT is offered for wellness and beauty and as an anti-aging strategy, in spite of the absence of studies on the cardiovascular system. Consequently, we investigated the impact of mHBOT on the cardiovascular system. Mechanical and energetic parameters of isolated heart submitted to ischemia/reperfusion injury and arterial contractile response from mHBOT-exposed rats were evaluated. In the heart, mHBOT increased pre-ischemic velocity of contraction and ischemic end-diastolic pressure and developed pressure and contractile economy during reperfusion. mHBOT decreased infarct size and increased the plasma nitrite levels. In the artery, mHBOT increased acetylcholine sensitivity. mHBOT protects the heart during ischemia/reperfusion and affects vascular relaxation.

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OBJECTIVE: To identify and characterize the population of Pediatric patients referred to our hyperbaric oxygen therapy center. METHODS: Retrospective and observational study, including pediatric patients treated with hyperbaric oxygen therapy, from 2006 to 2021, at the hyperbaric medicine reference center in the north of Portugal. Variables of interest were extracted from electronic medical records. RESULTS: Our study included 134 patients. The most frequent reasons for referral were carbon monoxide poisoning (n=59) and sudden sensorineural hearing loss (n=41). In 75 cases (56%), treatment was initiated in an urgent context. Symptom presentation at Emergency Department varied among patients, the most frequent being headache and nausea/vomiting. Concerning carbon monoxide poisoning, the most common sources were water heater, fireplace/brazier, and boiler. Regarding adverse effects, it was identified one case of intoxication by oxygen and four cases of middle ear barotrauma. CONCLUSIONS: The most frequent cause for referral was carbon monoxide poisoning. All patients evolved favorably, with few side effects being reported, emphasizing the safety of this therapy. While most pediatricians may not be aware of the potential benefits arising with hyperbaric oxygen therapy, it is of upmost importance to promote them, so that this technique is increasingly implemented.

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PURPOSE: The aim of this systematic review was to assess the role of hyperbaric oxygen therapy  (HBOT) in patients with dysphagia after radiation therapy for head and neck cancer. METHOD: A systematic search was conducted in the electronic databases Ovid MEDLINE, Ovid Embase, and Cochrane Central Register of Controlled Trials for relevant studies until March 14, 2023. No restriction on language or publication date. The criteria for inclusion: patients with HNC who had received both radiation therapy and HBOT as 1) a preventive treatment against swallowing difficulties, 2) to preserve swallowing function, or 3) to promote swallowing difficulties. RESULTS: We identified 1396 records. After removal of 31 duplicates, 1365 records were accessible for title and abstract screening. This yielded 53 studies for full text assessment. Six studies met the eligibility criteria and were included for qualitative analysis. CONCLUSION: Evidence of HBOT benefits in patients with dysphagia after radiation therapy for head and neck cancer is inconsistent. Well-designed studies using validated outcome measures and long-term follow-up are warranted.

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Introducción: La enfermedad descompresiva es un síndrome clínico complejo causado por la sobresaturación de gases respiratorios en la sangre y los tejidos, después de una reducción abrupta de la presión ambiental, que puede presentarse como parte de los accidentes de buceo. Dada su baja prevalencia se da a conocer una de sus formas de presentación en los servicios de urgencias, que requiere rapidez en el diagnóstico y conducta terapéutica inmediata. Objetivo: Presentar un caso grave de enfermedad descompresiva del oído interno. Caso clínico: Paciente masculino de 71 años de edad, buzo aficionado y antecedente de un accidente vascular encefálico isquémico hace aproximadamente 1 año. Realizó inmersiones, luego de las cuales comenzó a presentar síntomas como mareos, náuseas, vómitos copiosos, inestabilidad para la marcha y manifestaciones sensitivas en la cara. Horas después de ser evaluado en centro médico de urgencia, sin diagnóstico específico, se trasladó al cuerpo de guardia del hospital, para su valoración por el especialista en medicina subacuática. Conclusiones: La orientación diagnóstica de un paciente con enfermedad descompresiva requiere derivación urgente a un centro de tratamiento de enfermedades disbáricas(AU)

Introduction: Decompression illness is a complex clinical syndrome caused by supersaturation of respiratory gases in the blood and tissues, after an abrupt reduction in environmental pressure, which can occur as part of diving accidents. Given its low prevalence, one of its forms of presentation is revealed in emergency services, which requires speed in diagnosis and immediate therapeutic conduct. Objective: To present a severe case of decompressive disease of the inner ear. Clinical case: 71-year-old male patient, amateur diver, with a history of an ischemic stroke approximately 1 year ago. He performed dives, after which he began to present symptoms such as dizziness, nausea, copious vomiting, unsteadiness in walking, and sensitive manifestations on the face. Hours after being evaluated at the emergency medical center, without a specific diagnosis, he was transferred to the hospital's emergency room, for evaluation by the underwater medicine specialist. Conclusions: The diagnostic orientation of a patient with decompression illness requires urgent referral to a center for the treatment of dysbaric diseases(AU)

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INTRODUCTION: Cancer remains one of the leading causes of death worldwide, with 50-60% of patients requiring radiotherapy during the course of treatment. Patients' survival rate has increased significantly, with an inevitable increase in the number of patients experiencing side effects from cancer therapy. One such effect is late radiation injuries in which hyperbaric oxygen therapy appears as complementary treatment. With this work we intend to divulge the results of applying hyperbaric oxygen therapy among patients presenting radiation lesions in our Hyperbaric Medicine Unit. MATERIALS AND METHODS: Retrospective analysis of clinical records of patients with radiation lesions treated at the Hyperbaric Medicine Unit assessed by the scale Late Effects of Normal Tissues-Subjective, Objective, Management, Analytical (LENT-SOMA) before and after treatment, between October 2014 and September 2019 were included. Demographic characteristics, primary tumor site, subjective assessment of the LENT-SOMA scale before and after treatment were collected and a comparative analysis (Students t test) was done. RESULTS: 88 patients included: 33 with radiation cystitis, 20 with radiation proctitis, 13 with osteoradionecrosis of the mandible and 22 with radiation enteritis. In all groups, there was a significant decrease (p < 0.005) in the subjective parameter of the LENT-SOMA scale. DISCUSSION: Late radiation lesions have a major influence on patients' quality of life. In our study hyperbaric oxygen therapy presents as an effective therapy after the failure of conventional treatments. CONCLUSION: Hyperbaric oxygen therapy is an effective complementary therapy in the treatment of refractory radiation lesions.

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This study aimed to assess different approaches for bone healing evaluation on histological images and to introduce a new automatic evaluation method based on segmentation with distinct thresholds. We evaluated the hyperbaric oxygen therapy (HBO) effects on bone repair in type 1 diabetes mellitus rats. Twelve animals were divided into four groups (n = 3): non-diabetic, non-diabetic + HBO, diabetic, and diabetic + HBO. Diabetes was induced by intravenous administration of streptozotocin (50 mg/kg). Bone defects were created in femurs and HBO was immediately started at one session/day. After 7 days, the animals were euthanized, femurs were removed, demineralized, and embedded in paraffin. Histological sections were stained with hematoxylin and eosin (HE) and Mallory's trichrome (MT), and evaluated using three approaches: (1) conventional histomorphometric analysis (HE images) using a 144-point grid to quantify the bone matrix; (2) a semi-automatic method based on bone matrix segmentation to assess the bone matrix percentage (MT images); and (3) automatic approach, with the creation of a plug-in for ImageJ software. The time required to perform the analysis in each method was measured and subjected to Bland-Altman statistical analysis. All three methods were satisfactory for measuring bone formation and were not statistically different. The automatic approach reduced the working time compared to visual grid and semi-automated method (p < .01). Although histological evaluation of bone healing was performed successfully using all three methods, the novel automatic approach significantly shortened the time required for analysis and had high accuracy.

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PURPOSE: Management of Fournier's Gangrene (FG) includes broad-spectrum antibiotics with adequate surgical debridement, which should be performed within the first 24 hours of onset. However, this treatment may cause significant loss of tissue and may delay healing with the presence of ischemia. Hyperbaric oxygen therapy (HBOT) has been proposed as adjunctive therapy to assist the healing process. However, its benefit is still debatable. Therefore, this systematic review and meta-analysis aimed to evaluate the effect of HBOT as an adjunct therapy for FG. MATERIALS AND METHODS: This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocol to obtain studies investigating the effect of HBOT on patients with FG. The search is systematically carried out on different databases such as MEDLINE, Embase, and Scopus based on population, intervention, control, and outcomes criteria. A total of 10 articles were retrieved for qualitative and quantitative analysis. RESULTS: There was a significant difference in mortality as patients with FG who received HBOT had a lower number of deaths compared to patients who received conventional therapy (Odds Ratio 0.29; 95% CI 0.12 - 0.69; p = 0.005). However, the mean length of stay with Mean Difference (MD) of -0.18 (95% CI: -7.68 - 7.33; p=0.96) and the number of debridement procedures (MD 1.33; 95% CI: -0.58 - 3.23; p=0.17) were not significantly different. CONCLUSION: HBOT can be used as an adjunct therapy to prevent an increased risk of mortality in patients with FG.

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Background: Snakebites are the main responsible for envenoming in dogs and the bothropic venom remains the mostcommon in Brazil, which can induce a necrotic skin wound. Hyperbaric oxygen therapy (HBOT) use 100% oxygen underhigh pressure and used to treat different wounds in human patients. To the authors’ knowledge, no reports regarding to usethe HBOT in skin wound caused by snakebite (Bothrops jararaca) are present in the literature. The present clinical caseaimed to describe the use of HBOT for the treatment of an extensive necrotic wound caused by jararaca snakebite in a dog.Case: A neutered 8-year-old mixed-breed dog, weighing 12 kg, was admitted with a 7-day history of extensive necroticwound was identified in the face and neck causing by a snakebite, and no sign of pain. The procedure of HBOT (singlesessions of 1.5 ATM, 45 min, repeated every 48 h, up to 12 sessions) was decided, and the complete blood cells, alanineaminotransferase, creatinine, creatine kinase, prothrombin time, activated partial thromboplastin time, wound clinicalevaluation were measured at the following time-points: 2nd, 5th, 10th, and 12th sessions. At the 5th session was identifiedleukopenia, neutropenia and lymphopenia. Wound re-epithelialization was initiated after the 5th session, and the completeepithelialization was identified at the 12th session of HBOT. During the HBOT no side effects were identified. Threemonths after the HBOT finished, the animal returned to the clinic and the clinical status evolved positively, and the woundwas completed healed.Discussion: This report described the treatment of an extensive necrotic skin wound caused by snakebite (Bothrops jararaca)in an 8-year-old, neutered, mixed-breed dog using the HBOT. The wound healing...

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Background: Snakebites are the main responsible for envenoming in dogs and the bothropic venom remains the mostcommon in Brazil, which can induce a necrotic skin wound. Hyperbaric oxygen therapy (HBOT) use 100% oxygen underhigh pressure and used to treat different wounds in human patients. To the authors knowledge, no reports regarding to usethe HBOT in skin wound caused by snakebite (Bothrops jararaca) are present in the literature. The present clinical caseaimed to describe the use of HBOT for the treatment of an extensive necrotic wound caused by jararaca snakebite in a dog.Case: A neutered 8-year-old mixed-breed dog, weighing 12 kg, was admitted with a 7-day history of extensive necroticwound was identified in the face and neck causing by a snakebite, and no sign of pain. The procedure of HBOT (singlesessions of 1.5 ATM, 45 min, repeated every 48 h, up to 12 sessions) was decided, and the complete blood cells, alanineaminotransferase, creatinine, creatine kinase, prothrombin time, activated partial thromboplastin time, wound clinicalevaluation were measured at the following time-points: 2nd, 5th, 10th, and 12th sessions. At the 5th session was identifiedleukopenia, neutropenia and lymphopenia. Wound re-epithelialization was initiated after the 5th session, and the completeepithelialization was identified at the 12th session of HBOT. During the HBOT no side effects were identified. Threemonths after the HBOT finished, the animal returned to the clinic and the clinical status evolved positively, and the woundwas completed healed.Discussion: This report described the treatment of an extensive necrotic skin wound caused by snakebite (Bothrops jararaca)in an 8-year-old, neutered, mixed-breed dog using the HBOT. The wound healing...(AU)

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We investigated the local and systemic effects of hyperbaric oxygen therapy in BALB/C mice, exposed to two different exposure times, under 2.4 atmosphere (ATM). Fifteen animals were divided into three groups (GI, GII and Control) and underwent a surgical excision of a skin fragment of approximately one square centimeter of the dorsal region. The wounds were treated and monitored for 21 days. In the control group, the wound was cleaned once a day with sterile 0.9% NaCl solution. GI and GII mice were submitted to daily hyperbaric oxygen therapy of 30 or 60minutes sessions, respectively. The wounds were photographed every three days and their surfaces were analyzed by an image analyzer. At 21 days, all animals were euthanatized for histopathological analysis of the skin, lungs and liver in order to identify eventual alterations in wound healing or in the analyzed organs. Animals belonging to GI showed a faster skin wound healing in comparison to the other groups. Animals from GII, however, showed a delayed wound healing process and exhibited lung and microcirculatory alterations. These findings allow us to conclude that the exposure time to the oxygen in hyperbaric environment is crucial and can help or disturb skin wound healing or even be deleterious to other organs.(AU)

Investigaram-se os efeitos locais e sistêmicos da oxigenoterapia hiperbárica em camundongos BALB / C, submetidos a dois tempos de exposição diferentes, sob atmosfera 2,4 (ATM). Quinze animais foram divididos em três grupos (GI, GII e controle) e submetidos à excisão cirúrgica de fragmento de pele de aproximadamente um centímetro quadrado da região dorsal. As feridas foram tratadas e acompanhadas por 21 dias. No grupo controle, a ferida foi limpa uma vez ao dia, com solução estéril de NaCl 0,9%. Camundongos GI e GII foram submetidos à oxigenoterapia hiperbárica diária de 30 ou 60 minutos de sessões, respectivamente. As feridas foram fotografadas a cada três dias, e suas superfícies analisadas por um analisador de imagens. Aos 21 dias, todos os animais foram submetidos à eutanásia para análise histopatológica da pele, do pulmão e do fígado, em busca de eventuais alterações na cicatrização da ferida ou nos órgãos analisados. Animais pertencentes ao GI apresentaram cicatrização mais rápida de feridas cutâneas em comparação aos outros grupos. Já os animais do GII apresentaram retardo na cicatrização da ferida e alterações pulmonares e microcirculatórias. Esses achados permitem concluir que o tempo de exposição ao oxigênio em ambiente hiperbárico é fundamental e pode auxiliar ou atrapalhar a cicatrização de feridas cutâneas ou mesmo ser deletério para outros órgãos.(AU)

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We present two patients who developed visual deterioration due to carbon monoxide poisoning. They were treated with hyperbaric oxygen and recovered not only their vision but also they improved neurological signs and symptoms. We believe that implementation of hyperbaric oxygen, even in a late period of time will be effective in reversing neurological sequelae.

Se presentan dos pacientes que desarrollaron deterioro visual debido a una intoxicación por monóxido de carbono. Ellos fueron tratados con oxígeno hiperbárico y recuperaron no solo su visión, sino que, además, mejoraron su signo-sintomatología neurológica. Se cree que la implementación de oxígeno hiperbárico, incluso en un período tardío, será efectiva para revertir las secuelas neurológicas.

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PURPOSE: To investigate the effect of hyperbaric oxygen therapy on colonic anastomosis healing with and without ischemia in rats. METHODS: Forty female rats underwent segmental resection of 1 cm of the left colon followed by end-to-end anastomosis. They were randomly assigned to four groups (n=10 each), a sham group; two groups were submitted to Hyperbaric Oxygen therapy (HBOT) with and without induced ischemia and the induced ischemia group without HBOT. The HBOT protocol evaluated was 100% O2 at 2.4 Atmosphere absolute pressure (ATA) for 60 minutes, two sessions before as a preconditioning protocol and three sessions after the operation. Clinical course and mortality were monitored during all experiment and on the day of euthanasia on the fourth day after laparotomy. Macroscopic appearance of the abdominal cavity were assessed and samples for breaking strength of the anastomosis and histopathological parameters were collected. RESULTS: There was no statistically significant difference in mortality or anastomosis leak between the four experimental groups. Anastomosis breaking strength was similar across groups. CONCLUSION: The HBOT protocol tested herein at 2.4 ATA did not affect histopathological and biomechanical parameters of colonic anastomotic healing, neither the clinical outcomes death and anastomosis leak on the fourth day after laparotomy.

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OBJECTIVES: Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism. METHODS: SD rats were used to generate a type 2 diabetes model, which received stem cell therapy, HBO therapy, or both together. Before and after treatment, body weight, blood glucose, and serum insulin, blood lipid, pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and urinary proteins were measured and compared. After 6 weeks, rats were sacrificed and their organs were subjected to hematoxylin and eosin staining and immunofluorescence staining for insulin and glucagon; apoptosis and proliferation were analyzed in islet cells. Structural changes in islets were observed under an electron microscope. Expression levels of Pdx1, Ngn3, and Pax4 mRNAs in the pancreas were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In comparison with diabetic mice, those treated with the combination or SHE therapy showed decreased blood glucose, insulin resistance, serum lipids, and pro-inflammatory cytokines and increased body weight and serum insulin. The morphology and structure of pancreatic islets improved, as evident from an increase in insulin-positive cells and a decrease in glucagon-positive cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of islet cells revealed the decreased apoptosis index, while Ki67 and proliferating cell nuclear antigen staining showed increased proliferation index. Pancreatic expression of Pdx1, Ngn3, and Pax4 was upregulated. CONCLUSION: SHED combined with HBO therapy was effective for treating type 2 diabetic rats. The underlying mechanism may involve SHED-mediated increase in the proliferation and trans-differentiation of islet ß-cells and decrease in pro-inflammatory cytokines and apoptosis of islets.

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Introducción: La gangrena de Fournier es una enfermedad infecciosa caracterizada por una fascitis necrotizante de evolución fulminante que afecta a la región perineal, genital o perianal, con una rápida progresión y alta letalidad. Objetivo: Describir la sintomatología del paciente y buena evolución, a pesar de varios factores de mal pronóstico. Caso clínico: Se trata de un paciente masculino de 77 años de edad, diabético e hipertenso, remitido a cuidados intensivos, desde el servicio de Urología, con el diagnóstico de gangrena de Fournier, descontrol metabólico y agudización de su enfermedad renal crónica. Conclusiones: Con el tratamiento médico quirúrgico intensivo y la utilización de oxigenación hiperbárica, tuvo una evolución favorable, hasta su egreso(AU)

Introduction: Fournier gangrene is an infectious disease characterized by a necrotizing fascitis of fulminant evolution that affects the perineal, genital or perianal region, with rapid progression and high lethality. Objective: To describe the patient symptomatology and good evolution, despite several factors of poor prognosis. Clinical case: 77-year-old male patient, diabetic and hypertensive, referred to intensive care, from the urology department, with the diagnosis of Fournier gangrene, metabolic decontrol and exacerbation of chronic kidney disease. Conclusions: With intensive surgical and medical treatment and the use of hyperbaric oxygenation, he had a favorable evolution, until his discharge(AU)

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Systemic arterial air embolism (SAAE) is a rare but potentially life-threatening condition that may occur when air enters into pulmonary veins or directly into the systemic circulation after pulmonary procedures (biopsy or resection) or penetrating trauma to the lung. While venous air embolism is commonly reported, arterial air embolism is rare. Even a minor injury to the chest along with positive-pressure ventilation can cause SAAE. Small amounts of air may cause neurological or cardiac symptoms depending on the affected arteries, while massive embolism can result in fatal cardiovascular collapse. We discuss the various causes of SAAE, including trauma, computed tomography-guided lung biopsy, and various intervention procedures such as mechanical circulatory support device implantation, coronary catheterization, and atrial fibrillation repair. SAAE diagnosis can be overlooked because its symptoms are not specific, and confirmation of the presence of air in the arterial system is difficult. Although computed tomography is the optimal imaging tool for diagnosis, patient instability and resuscitation often precludes its use. When imaging is performed, awareness of the causes of SAAE allows the radiologist to promptly diagnose the condition and relay findings to the clinicians so that treatment, namely hyperbaric oxygen therapy, may be started promptly.

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Abstract Purpose To investigate the effect of hyperbaric oxygen therapy on colonic anastomosis healing with and without ischemia in rats. Methods Forty female rats underwent segmental resection of 1 cm of the left colon followed by end-to-end anastomosis. They were randomly assigned to four groups (n=10 each), a sham group; two groups were submitted to Hyperbaric Oxygen therapy (HBOT) with and without induced ischemia and the induced ischemia group without HBOT. The HBOT protocol evaluated was 100% O2 at 2.4 Atmosphere absolute pressure (ATA) for 60 minutes, two sessions before as a preconditioning protocol and three sessions after the operation. Clinical course and mortality were monitored during all experiment and on the day of euthanasia on the fourth day after laparotomy. Macroscopic appearance of the abdominal cavity were assessed and samples for breaking strength of the anastomosis and histopathological parameters were collected. Results There was no statistically significant difference in mortality or anastomosis leak between the four experimental groups. Anastomosis breaking strength was similar across groups. Conclusion The HBOT protocol tested herein at 2.4 ATA did not affect histopathological and biomechanical parameters of colonic anastomotic healing, neither the clinical outcomes death and anastomosis leak on the fourth day after laparotomy.

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OBJECTIVES: Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism. METHODS: SD rats were used to generate a type 2 diabetes model, which received stem cell therapy, HBO therapy, or both together. Before and after treatment, body weight, blood glucose, and serum insulin, blood lipid, pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and urinary proteins were measured and compared. After 6 weeks, rats were sacrificed and their organs were subjected to hematoxylin and eosin staining and immunofluorescence staining for insulin and glucagon; apoptosis and proliferation were analyzed in islet cells. Structural changes in islets were observed under an electron microscope. Expression levels of Pdx1, Ngn3, and Pax4 mRNAs in the pancreas were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In comparison with diabetic mice, those treated with the combination or SHE therapy showed decreased blood glucose, insulin resistance, serum lipids, and pro-inflammatory cytokines and increased body weight and serum insulin. The morphology and structure of pancreatic islets improved, as evident from an increase in insulin-positive cells and a decrease in glucagon-positive cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of islet cells revealed the decreased apoptosis index, while Ki67 and proliferating cell nuclear antigen staining showed increased proliferation index. Pancreatic expression of Pdx1, Ngn3, and Pax4 was upregulated. CONCLUSION: SHED combined with HBO therapy was effective for treating type 2 diabetic rats. The underlying mechanism may involve SHED-mediated increase in the proliferation and trans-differentiation of islet β-cells and decrease in pro-inflammatory cytokines and apoptosis of islets.

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