Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice.

BACKGROUND: Radiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individually or in combination therapy, in mitigating RISF. METHODS: Using a female C57BL/6J mouse model subjected to hind limb irradiation as a representative RISF model, we evaluated metformin, ASCs, or their combination in two contexts: prophylactic (started on day 1 post-irradiation) and therapeutic (initiated on day 14 post-irradiation, coinciding with fibrosis symptoms). We measured limb movement, examined skin histology, and analyzed gene expression to assess treatment efficacy. RESULTS: Prophylactic metformin and ASCs, whether autologous or allogeneic, effectively prevented late fibrosis, with metformin showing promising results. However, combination therapy did not provide additional benefits when used prophylactically. Autologous ASCs, alone or with metformin, proved most effective against late-stage RISF. Prophylactic intervention outperformed late therapy for mitigating radiation skin damage. Co-culture studies revealed that ASCs and metformin downregulated inflammation and fibrotic gene expression in both mouse and human fibroblasts. CONCLUSIONS: Our study suggests metformin's potential as a prophylactic measure to prevent RISF, and the combination of ASCs and metformin holds promise for late-stage RISF treatment. These findings have clinical implications for improving the quality of life for those affected by radiation-induced skin fibrosis.

Surgical Correction of True Diphallia in a Newborn Male.

Diphallia is an exceedingly rare anomaly characterized by partial or complete duplication of the phallus. Approximately 100 cases have been reported worldwide since its initial documentation, and incidence is estimated at 1 in 5 to 6 million live births. Therapeutic management is dependent on the extent of the anomaly, ranging from phallic excision to complex reconstructive procedures in cases of broader systemic involvement. We present the case of congenital true diphallia with associated penoscrotal transposition, bifid scrotum, partial urethral duplication, ventral chordee, large scrotal lipoma and sacral dimple. We further present a review of available literature pertaining to diphallia.

Allogeneic adipose-derived stem cells mitigate acute radiation syndrome by the rescue of damaged bone marrow cells from apoptosis.

Acute radiation syndrome (ARS) is the radiation toxicity that can affect the hematopoietic, gastrointestinal, and nervous systems upon accidental radiation exposure within a short time. Currently, there are no effective and safe approaches to treat mass population exposure to ARS. Our study aimed to evaluate the therapeutic potential of allogeneic adipose-derived stem cells (ASCs) for total body irradiation (TBI)-induced ARS and understand the underlying mitigation mechanism. We employed 9.25 Gy TBI dose to C57BL/6 mice and studied the effect of allogeneic ASCs on mice survival and regeneration of the hematopoietic system. Our results indicate that intraperitoneal-injected ASCs migrated to the bone marrow, rescued hematopoiesis, and improved the survival of irradiated mice. Our transwell coculture results confirmed the migration of ASCs to irradiated bone marrow and rescue hematopoietic activity. Furthermore, contact coculture of ASCs improved the survival and hematopoiesis of irradiated bone marrow in vitro. Irradiation results in DNA damage, upregulation of inflammatory signals, and apoptosis in bone marrow cells, while coculture with ASCs reduces apoptosis via activation of DNA repair and the antioxidation system. Upon exposure to irradiated bone marrow cells, ASCs secrete prosurvival and hematopoietic factors, such as GM-CSF, MIP1α, MIP1ß, LIX, KC, 1P-10, Rantes, IL-17, MCSF, TNFα, Eotaxin, and IP-10, which reduces oxidative stress and rescues damaged bone marrow cells from apoptosis. Our findings suggest that allogeneic ASCs therapy is effective in mitigating TBI-induced ARS in mice and may be beneficial for clinical adaptation to treat TBI-induced toxicities. Further studies will help to advocate the scale-up and adaptation of allogeneic ASCs as the radiation countermeasure.

Prenatally Diagnosed Testicular Torsion: A Rare Condition That Causes Dilemma in Management.

BACKGROUND: Prenatal testicular torsion (PTT) is exceedingly rare in intrauterine development, often diagnosed at the time of birth and very rarely diagnosed in utero during routine gestational ultrasound. As a result, incidence is unknown, and there exists no consensus regarding the pathophysiology of this phenomenon nor universally recognized algorithms and guidelines regarding its diagnosis and management. Case Presentation. We present the case of an antenatally diagnosed torsion and our subsequent management which included ipsilateral orchiectomy and prophylactic contralateral orchiopexy via a scrotal approach. CONCLUSION: While controversy regarding surgical intervention in patients with unilateral PTT exists due to poor salvage rates-estimated to be less than 1%-the risk of anorchia is higher in affected patients due to limitations in the accuracy of detecting bilateral testicular involvement. Risk of misdiagnosis of bilaterality may lead to lasting sequelae such as infertility and devastating psychological consequences for affected patients, supporting the need for surgical exploration, as was performed in our case.