The role of necroptosis in neurosurgical diseases

Programmed necrosis or necroptosis is an alternative form of cell death that is executed through a caspase-independent pathway. Necroptosis has been implicated in many pathological conditions. Genetic or pharmacological inhibition of necroptotic signaling has been shown to confer neuroprotection after traumatic and ischemic brain injury. Therefore, the necroptotic pathway represents a potential target for neurological diseases that are managed by neurosurgeons. In this review, we summarize recent advances in the understanding of necroptotic signaling pathways and explore the role of necroptotic cell death in craniocerebral trauma, brain tumors, and cerebrovascular diseases.

Role of Sphk1 in the malignant transformation of breast epithelial cells and breast cancer progression.

BACKGROUND: The ojective of the following study is to investigate the role of sphingosine kinase 1 (Sphk1) in the malignant transformation of breast epithelial cells and breast cancer progression and its mechanism. MATERIALS AND METHODS: Immunohistochemistry was performed to detect Sphk1 and E‑cadherin (E‑cad) in resected breast samples. Sphk1 was transfected in normal human breast epithelial cell line (MCF‑10A) by Lentivirus and silenced in breast cancer cell line (MCF‑7) using small interfering ribonucleic acid. The effect of tumor necrosis factor alpha (TNF‑α) and/or N, N‑dimethylsphingosine (DMS) on the Sphk1 and E‑cad expression, MCF‑10A cell proliferation and invasion was investigated. Real time‑polymerase chain reaction and western‑blot was used to detect messenger ribonucleic acid and protein. Cell counting kit‑8 and transwell were used to measure cell proliferation and invasion. RESULTS: Sphk1 was positive expression in 114 breast tumors (75.50%) but negative in fibroadenomas. The expression of E‑cad and Sphk1 were negatively correlated and E‑cad (−)/Sphk1 (+) carriers showed higher ratio of axillary lymph node metastasis than E‑cad (+)/Sphk1 (−) carriers. Overexpression of Sphk1 in MCF‑10A reduced E‑cad expression and improved cell proliferation and invasion, but knockdown of Sphk1 in MCF‑7 decreased cell proliferation and invasion. TNF‑α increased Sphk1 expression, enhanced the ability of Sphk1 in decreasing E‑cad expression, which could be blocked by DMS. TNF‑α promoted MCF‑10A cell proliferation and invasion.CONCLUSION: Sphk1 plays an important role in the malignant transformation of breast epithelial cells and modulates breast cancer metastasis through the regulation of E‑cad expression. TNF‑α can up‑regulate Sphk1 expression and reduce E‑cad expression through Sphk1, which can be blocked by DMS. TNF‑α/Sphk1/E‑cad pathway may be a newly discovered pathway and plays an important role in tumorigenesis and metastasis.

The impact of short daily hemodialysis on anemia and the quality of life in Chinese patients

Anemia is a frequent complication in hemodialysis patients. Compared to conventional hemodialysis (CHD), short daily hemodialysis (sDHD) has been reported to be effective in many countries except China. The aim of the present study was to determine whether sDHD could improve anemia and quality of life (QOL) for Chinese outpatients with end-stage renal disease. Twenty-seven patients (16 males/11 females) were converted from CHD to sDHD. All laboratory values were measured before conversion (baseline), at 3 months after conversion (sDHD1), and at 6 months after conversion (sDHD2). The patient's QOL was evaluated at baseline and 6 months after conversion using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Hemoglobin concentration increased significantly from 107.4±7.9 g/L at baseline to 114.4±6.8 g/L (P<0.05) at sDHD1, and 118.3±8.4 g/L (P<0.001) at sDHD2 (Student paired t-test). However, the dose requirement for erythropoietin decreased from 6847.8±1057.3 U/week at baseline to 5869.6±1094.6 U/week (P<0.05) at sDHD2. Weekly stdKt/V increased significantly from 2.05±0.13 at baseline to 2.73±0.20 (P<0.001) at sDHD1, and 2.84±0.26 (P<0.001) at sDHD2. C-reactive protein decreased from baseline to sDHD1 and sDHD2, but without statistically significant differences. Physical and mental health survey scores increased in the 6 months following conversion to sDHD. sDHD may increase hemoglobin levels, decrease exogenous erythropoietin dose requirements, and improve QOL in Chinese hemodialysis patients compared to CHD. A possible mechanism for improvement of clinical outcomes may be optimized management of uremia associated with the higher efficiency of sDHD.

Transplantation of fibula with vascular pedicle for fusion of ankle in leprotic drop-foot.

Devascularized bone grafts are pieces of dead bone and they simply serve as scaffolds for new bone to grow and fill the gap, taking a long time when they succeed in doing so. In contrast, vascularized grafts being living tissues have short healing time, great vitality and strong infection-resisting capacity. We report here the successful use of vascularized grafts of the lower end of fibula for fusing the ankle in five leprosy patients.

Techniques for covering soft tissue defects resulting from plantar ulcers in leprosy: Part V. Use of the flap in the inguinal region and latissimus dorsi musculocutaneous flap.

The area of distribution of the superficial circumflex iliac, superficial epigastric and superficial external pudental arteries is large and flaps based on them can meet the requirement of different recipient sites. We have transplanted free flaps based on the superficial epigastric artery for repairing plantar soft tissue defects in six leprosy patients. During the follow-up examination 58 to 118 months later there has been no recurrence of ulceration in any of these cases. The latissimus dorsi muscle, is mainly nourished by the thoracadorsal artery and the latissimus dorsi musculocutaneous flap is a large sized, composite structure with abundant blood provision and strong anti-infectious property. The latissimus dorsi flap can be used as an artery-pedicled island flap or as a free flap besides its use as a muscle graft, because of its constant vascular position, wide outer-diameter of the vessels and long pedicle. It can therefore be utilized for repairing soft tissue defect or replacement of paralyzed muscle. We have used the latissimus dorsi musculocutaneous free flap for repairing large skin and soft tissue defects resulting from plantar ulceration in three leprosy patients. During the follow-up period, one patient who had complete drop-foot and had refused corrective surgery had recurrence of the ulcer in the 12th post-operative month. No ulcers had recurred in the other two cases during the follow-up at 48 and 114 months.

Techniques for covering soft tissue defects resulting from plantar ulcers in leprosy: Part IV. Use of medial leg flap and medial knee flap.

The medial leg flap, based on the cutaneous branches of the posterior tibial artery is raised from the middle and lower regions of the medial aspect of the leg. It has a long pedicle, and it can be used as a free flap to reconstruct the distant soft tissue defects and also as an island flap. We have used this retrograde island flap for surfacing ulcerated areas in six leprosy patients. The flap survived in all cases. At 24 to 60 months follow-up examination, ulceration had not recurred in any of them. The medial knee flap consisting of the skin and subcutaneous tissue of the lower part of the medial side of the thigh and the upper part of the leg, is suitable for covering soft tissue cushion defects of the extremities because of the constant vessels, long pedicle, wide diameter, well-recognizable sensory nerves and less subcutaneous fat. We have used the medial knee flap for the resurfacing sizeable raw areas due to ulceration in three leprosy patients. The flap survived in all cases and there was no recurrence of ulceration during the 70-148 months follow-up period.

Techniques for covering soft tissue defects resulting from plantar ulcers in leprosy: Part II--First toe web and dorsal foot flaps.

The first toe web flap consists of the skin and subcutaneous tissues of the contiguous sides between the great and second toes. It is based on the first dorsal metatarsal artery or the common plantar digital artery. This flap was used as artery pedicled island graft to reconstruct losses of skin and soft tissue cushion in the ball of the foot in the first and second metatarsal head region in 16 cases. Follow-up examination revealed that ulceration had recurred in one case due to dehiscence of the flap margin 12 months post-operatively. The other 15 patients have done well without recurrence at 48 to 124 months follow-up examination. The dorsal flap of the foot based on the dorsalis pedis artery, the corresponding veins and the deep peroneal nerve was designed in 1974 to resurface skin and soft tissue defects in the sole of the foot. This flap was used in 30 cases of leprosy with excellent results. During follow-up 36 to 120 months after surgery the plantar ulcer had recurred in only one case. All the others have done well. The long-term curative effect has thus proved satisfactory.

Techniques for covering soft tissue defects resulting from plantar ulcers in leprosy: Part I--General considerations and summary of results.

Recurrent plantar ulceration is a common and serious complication occurring consequent to impairment of the tibial nerve in leprosy patients. In spite of many therapies and long therapeutic course, it is extremely difficult to abolish this complication in many cases because of extensive skin and soft tissue cushion loss due to repeated infection. Since the early 70's we have been using microscopic surgical techniques to reconstruct the ulcerated area using eight types of the flaps. In this series of papers we review our experience (76 patients). Post-operatively, the flaps survived in all cases, the long-term results have proved satisfactory, and recurrent ulceration occurred in only three patients.

A rapid activation of immature testis of Japanese eel (Anguilla japonica) by a single injection of human chorionic gonadotropin.

The testis of Japanese eel (Anguilla japonica) consists of type A and early type B spermatogonia together with inactive Leydig and Sertoli cells. A single injection of human chorionic gonadotropin induced marked changes in the morphology of the testis and in the scrum androgen levels within a period of 72 h. Morphological changes include spermatogonial proliferation, activation of Leydig and Sertoli cells, organization of seminiferous lobules and formation of lobular lumen in the testis. Leydig cells were enlarged, exhibiting characteristics of steroid-producing cells. Sertoli cells become elongated, show signs of high cellular activity and remain in close contact with spermatogonia. The lobular organization was achieved much earlier than the progression of spermatogenesis to late type Β spermatogonia. Even 6 h after hCG injection, a significant increase in plasma levels of 11-ketotestosterone was observed, followed by a further time dependent increase. Plasma testosterone levels were also increased after injection, but the increase was much less than that of 11-ketotestosterone.