Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy

Jin, Hua,Piao, Shang Guo,Jin, Ji Zhe,Jin, Ying Shun,Cui, Zhen Hua,Jin, Hai Feng,Zheng, Hai Lan,Li, Jin Ji,Jiang, Yu Ji,Yang, Chul Woo,Li, Can S.Karger 2014 The Nephron Journals Vol.126 No.3

<P>Abstract</P><P><B><I>Background:</I></B> Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. <B><I>Methods:</I></B> Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of both. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors [transforming growth factor-β<SUB>1</SUB> (TGF-β<SUB>1</SUB>) and connective tissue growth factor (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. <B><I>Results:</I></B> Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β<SUB>1</SUB> and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. <B><I>Conclusions:</I></B> LEF treatment lessens DN, and combined treatment with LEF and benazepril provides synergistic effects in preventing DN.</P><P>© 2014 S. Karger AG, Basel</P>

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

( Yu Ji Jiang ),( Sheng Cui ),( Kang Luo ),( Jun Ding ),( Qi Yan Nan ),( Shang Guo Piao ),( Mei Ying Xuan ),( Hai Lan Zheng ),( Yong Jie Jin ),( Ji Zhe Jin ),( Jung Pyo Lee ),( Byung Ha Chung ),( Bum 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.6

Background/Aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal in-jury. Methods: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). Results: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinflammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. Conclusions: Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction

( Hai Yan Zhao ),( Hui Ying Li ),( Jian Jin ),( Ji Zhe Jin ),( Long Ye Zhang ),( Mei Ying Xuan ),( Xue Mei Jin ),( Yu Ji Jiang ),( Hai Lan Zheng ),( Ying Shun Jin ),( Yong Jie Jin ),( Bum Soon Choi ) 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.0

Background/Aims: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Methods: Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H₂O₂-exposed human kidney cells (HK-2) were treated with LC. Results: LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H₂O₂-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. Conclusions: LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

CHAOTIC MOTION OF A RESTRAINED PIPE CONVEYING FLUID

Ji-Duo Jin,Zhe-Qing Yang 한국소음진동공학회 1997 한국소음진동공학회 국제학술대회논문집 Vol.1997 No.1

Umbilical cord vessels other than the umbilical arteries and vein: a histological study of midterm human fetuses

Ji Hyun Kim,Shogo Hayashi,Zhe Wu Jin,Gen Murakami,José Francisco Rodríguez Vázquez 대한해부학회 2022 Anatomy & Cell Biology Vol.55 No.4

At birth, the umbilical cord contains various types of thin vessels that are near and outside the umbilicus and separate from the umbilical arteries and vein. These vessels are regarded as the remnant “vitelline vessels” and are often called “umbilical vessels”, although this terminology could lead to confusion with the true umbilical arteries and vein. No study has yet comprehensively examined these vessels using histological sections. Our examination of these vessels in 25 midterm fetuses (gestational age: 10–16 weeks) led to five major findings: (i) all specimens had umbilical branches of the inferior epigastric artery; (ii) 5 specimens had vitelline vein remnants; (iii) 4 specimens had a thin artery originating from the left hepatic artery that ran along the umbilical vein; (iv) 2 specimens had a so-called “para-umbilical vein” that was along the umbilical vein and reached the umbilicus; and (v) all specimens had lymphatic vessels originating from the umbilicus that ran caudally along the umbilical artery. The pelvic vein tributaries were well developed along the intra-abdominal umbilical artery, but did not reach the umbilicus. The lymphatic vessel was distinguished from the veins by an intraluminar cluster of lymphocytes attaching to the endothelium. The arterial branch in the umbilical cord did not accompany veins and lymphatic vessels, in contrast to the mother artery in the rectus abdominis. All these thin vessels seemed to be obliterated when the fibrous umbilical ring grew during late-term. The para-umbilical collateral vein in adults might develop outside the fibrous umbilical ring after birth.

Chaotic Motion of a Restrained Pipe Conveying Fluid

Ji Duo Jin,Zhe Qing Yang 대한기계학회 1997 Asia-Pacific Vibration Conference Vol.1 No.1

Topographical relationships of the yolk sac remnant and vitelline vessels with the midgut loop in the extra-embryonic coelom of human embryos

Zhe-Wu Jin,Ji Hyun Kim,Masahito Yamamoto,Gen Murakami,Shin-ichi Abe,José Francisco Rodríguez-Vázquez 대한해부학회 2022 Anatomy & Cell Biology Vol.55 No.3

The yolk sac is supplied by the vitelline artery and vein (VA, VV), which run through the yolk stalk in combination with the omphaloenteric duct. Moreover, the VV takes a free posterior course outside the midgut mesentery containing the secondarily-developed superior mesenteric vein (SMV). However, the regression process of these structures has not been demonstrated photographically. The present study evaluated serial histological sections from 20 embryos of stages 15–19 or crown-rump length (CRL) 7.5–20 mm. All specimens carried the SMV as sequential tissue slits. However, an omphaloenteric duct with epithelia continuous with the midgut loop was not observed. In smaller embryos (CRL <13 mm) the VA extended distally or anteriorly from the midgut apex in the extra-embryonic coelom, whereas in larger embryos (CRL 16–20 mm) the artery was absent from the distal side of the apex. The entire course or part of the VV outside the mesentery was always seen, but four larger embryos lacked the venous terminal near the duodenum. A vacuole-like remnant of the yolk sac was present in all smaller embryos (CRL <10 mm), but was absent from 7 of the 11 larger embryos. The size of the remnant was equal to the thickness of the VA or VV, with the remnant being sandwiched between the VA and VV. Moreover, the regressing yolk sac often communicated with or opened to the VV. Consequently, the yolk sac regressed first, followed by the regression of the VA until 6 weeks. The yolk stalk was clearly observed until 5 weeks.

Development and growth of the human fetal sacroiliac joint revisited: a comparison with the temporomandibular joint

Ji Hyun Kim,Zhe Wu Jin,Shogo Hayashi,Gen Murakami,Hiroshi Abe,José Francisco Rodríguez Vázquez 대한해부학회 2023 Anatomy & Cell Biology Vol.56 No.2

The human fetal sacroiliac joint (SIJ) is characterized by unequal development of the paired bones and delayedcavitation. Thus, during the long in utero period, the bony ilium becomes adjacent to the cartilaginous sacrum. This mor­phology may be analogous to that of the temporomandibular joint (TMJ). We examined horizontal histological sections of 24 fetuses at 10–30 weeks and compared the timing and sequences of joint cartilage development, cavitation, and ossification of the ilium. We also examined histological sections of the TMJ and humeroradial joint, because these also contain a disk or disk-like structure. In the ilium, endochondral ossification started in the anterior side of the SIJ, extended posteriorly and reached the joint at 12 weeks GA, and then extended over the joint at 15 weeks GA. Likewise, the joint cartilage appeared at the anterior end of the future SIJ at 12 weeks GA, and extended along the bony ilium posteriorly to cover the entire SIJ at 26 weeks GA. The cavitation started at 15 weeks GA. Therefore, joint cartilage development seemed to follow the ossification of the ilium by extending along the SIJ, and cavitation then occurred. This sequence “ossification, followed by joint cartilage formation, and then cavitation” did not occur in the TMJ or humeroradial joint. The TMJ had a periosteum-like membrane that covered the joint surface, but the humeroradial joint did not. After muscle contraction starts, it is likely that the mechanical stress from the bony ilium induces development of joint cartilage.

Persistent right umbilical vein: a study using serial sections of human embryos and fetuses

Ji Hyun Kim,Zhe Wu Jin,Gen Murakami,Ok Hee Chai,José,Francisco Rodrí,guez-Vá,zquez 대한해부학회 2018 Anatomy & Cell Biology Vol.51 No.3

Persistent right umbilical vein (PRUV) is a common anomaly of the venous system. Although candidates for future PRUV were expected to occur more frequently in earlier specimens, evaluation of serial horizontal sections from 58 embryos and fetuses of gestational age 5‒7 weeks found that only two of these embryos and fetuses were candidates for anomalies. In a specimen, a degenerating right umbilical vein (UV) joined the thick left UV in a narrow peritoneal space between the liver and abdominal cavity, and in the other specimen, a degenerating left UV joined a thick right UV in the abdominal wall near the liver. In these two specimens, the UV drained into the normal, umbilical portion of the left liver. These results strongly suggested that, other than the usual PRUV draining into the right liver, another type of PRUV was likely to consist of the right UV draining into the left liver.

Relationship of the fabella with the origins of the plantaris and gastrocnemius lateral head muscles in late-term fetuses: a histological study

Zhe-Wu Jin,Ji Hyun Kim,Daisuke Suzuki,Namiko Sugai,Gen Murakami,Hiroshi Abe,José,Francisco Rodrí,guez-Vá,zquez 대한해부학회 2021 Anatomy & Cell Biology Vol.54 No.2

Previous studies of midterm fetuses indicated that a cartilaginous fabella appeared to be embedded in the plantaris (PL), and was fused with the gastrocnemius lateral head (GL). We re-examined the topographical anatomy of the fabella or its analogue (a tight fibrous mass) originating in the GL and/or PL by evaluating histological sections of the unilateral knees of 15 late-term fetuses. Regardless of whether the cartilaginous fabella was present (6 fetuses) or absent (9 fetuses), the origins of the PL and GL muscles each had three parts. In each fetus, the fabella or its analogue was embedded in a thick common tendinous origin of the GL and PL. PL1 (whose origin is similar to that of the adult PL) originated from the femoral condyle immediately above the common tendon; PL2 originated from the posteromedial aspect of the fabella or its analogue; and PL3 originated from the inferior aspect of the fabella or its analogue. The muscle fibers of PL1, PL2, and PL3 joined to provide a thick plantaris. GL1 (which is adjacent to PL2) originated from the common tendon in the superior side of the fabella or its analogue and GL2 originated from the inferior side of the fabella or its analogue. GL1 and GL2 joined to provide a thick bundle, whereas GL3 (located far below the fabella or its analogue) originated from the posterior surface aponeurosis. Therefore, drastic reconstruction at these muscle origins was necessary during development. Due to the strong mechanical stress from the GL and the space-occupying effect of the muscle, we hypothesize that PL2 and PL3 are degraded or absorbed into the GL1 and GL2 during the postnatal period, so that the remaining PL1 was likely the remaining PL in adults.