A new direction in Chinese herbal medicine ameliorates for type 2 diabetes mellitus: Focus on the potential of mitochondrial respiratory chain complexes.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes is a common chronic disease. Chinese herbal medicine (CHM) has a history of several thousand years in the treatment of diabetes, and active components with hypoglycemic effects extracted from various CHM, such as polysaccharides, flavonoids, terpenes, and steroidal saponins, have been widely used in the treatment of diabetes. AIM OF THE STUDY: Research exploring the potential of various CHM compounds to regulate the mitochondrial respiratory chain complex to improve type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The literature data were primarily obtained from authoritative databases such as PubMed, CNKI, Wanfang, and others within the last decade. The main keywords used include "type 2 diabetes mellitus", "Chinese medicine", "Chinese herbal medicine", "mitochondrial respiratory chain complex", and "mitochondrial dysfunction". RESULTS: Chinese herbal medicine primarily regulates the activity of mitochondrial respiratory chain complexes in various tissues such as liver, adipose tissue, skeletal muscle, pancreatic islets, and small intestine. It improves cellular energy metabolism through hypoglycemic, antioxidant, anti-inflammatory and lipid-modulating effects. Different components of CHM can regulate the same mitochondrial respiratory chain complexes, while the same components of a particular CHM can regulate different complex activities. The active components of CHM target different mitochondrial respiratory chain complexes, regulate their aberrant changes and effectively improve T2DM and its complications. CONCLUSION: Chinese herbal medicine can modulate the function of mitochondrial respiratory chain complexes in various cell types and exert their hypoglycemic effects through various mechanisms. CHM has significant therapeutic potential in regulating mitochondrial respiratory chain complexes to improve T2DM, but further research is needed to explore the underlying mechanisms and conduct clinical trials to assess the safety and efficacy of these medications. This provides new perspectives and opportunities for personalized improvement and innovative developments in diabetes management.

Unveiling OSCP as the potential therapeutic target for mitochondrial dysfunction-related diseases.

Mitochondria are important organelles in cells responsible for energy production and regulation. Mitochondrial dysfunction has been implicated in the pathogenesis of many diseases. Oligomycin sensitivity-conferring protein (OSCP), a component of the inner mitochondrial membrane, has been studied for a long time. OSCP is a component of the F1Fo-ATP synthase in mitochondria and is closely related to the regulation of the mitochondrial permeability transition pore (mPTP). Studies have shown that OSCP plays an important role in cardiovascular disease, neurological disorders, and tumor development. This review summarizes the localization, structure, function, and regulatory mechanisms of OSCP and outlines its role in cardiovascular disease, neurological disease, and tumor development. In addition, this article reviews the research on the interaction between OSCP and mPTP. Finally, the article suggests future research directions, including further exploration of the mechanism of action of OSCP, the interaction between OSCP and other proteins and signaling pathways, and the development of new treatment strategies for mitochondrial dysfunction. In conclusion, in-depth research on OSCP will help to elucidate its importance in cell function and disease and provide new ideas for the treatment and prevention of related diseases.

Ion beam figuring approach for thermally sensitive space optics.

During the ion beam figuring (IBF) of a space mirror, thermal radiation of the neutral filament and particle collisions will heat the mirror. The adhesive layer used to bond the metal parts and the mirror is very sensitive to temperature rise. When the temperature exceeds the designed value, the mirror surface shape will change markedly because of the thermal deformation and stress release of the adhesive layer, thereby reducing the IBF accuracy. To suppress the thermal effect, we analyzed the heat generation mechanism. By using thermal radiation theory, we established a thermal radiation model of the neutral filament. Additionally, we acquired a surface-type Gaussian heat source model of the ion beam sputtering based on the removal function and Faraday scan result. Using the finite-element-method software ABAQUS, we developed a method that can simulate the thermal effect of the IBF for the full path and all dwell times. Based on the thermal model, which was experimentally confirmed, we simulated the thermal effects for a 675 mm×374 mm rectangular SiC space mirror. By optimizing the dwell time distribution, the peak temperature value of the adhesive layer during the figuring process was reduced under the designed value. After one round of figuring, the RMS value of the surface error changed from 0.094 to 0.015λ (λ=632.8 nm), which proved the effectiveness of the thermal analysis and suppression method.

TNF-α mediates increased susceptibility to ischemic AKI in diabetes.

Diabetes is a risk factor for the development of acute kidney injury (AKI) in humans and rodents. However, the mechanistic basis for this observation is unknown. The present studies evaluated the role of inflammation and TNF-α in ischemic AKI in a model of type 2 diabetes mellitus (DM). Diabetic (db/db) and nondiabetic (db/+) littermates were subjected to 20 min of bilateral renal ischemia. The nondiabetic mice developed only mild and transient renal dysfunction. In contrast, the equivalent ischemic insult provoked severe and sustained renal dysfunction in the db/db mice. The expression of TNF-α and Toll-like receptor 4 (TLR4) mRNA was measured in the kidneys of diabetic mice before and after renal ischemia; db/db mice exhibited greater increases in TNF-α and TLR4 mRNA expression following ischemia than did db/+. In addition, urinary excretion of TNF-α after ischemia was higher in db/db mice than in db/+ mice. To determine the possible role of TNF-α in mediating the enhanced susceptibility of diabetic mice to ischemic injury, db/db mice were injected with either a neutralizing anti-mouse TNF-α antibody or nonimmune globulin and then subjected to 20 min of bilateral renal ischemia. Treatment of the db/db mice with the TNF-α antibody provided significant protection against the ischemic injury. These data support the view that diabetes increases the susceptibility to ischemia-induced renal dysfunction. This increased susceptibility derives from a heightened inflammatory response involving TNF-α and perhaps TLR4 signaling.

Focusing properties of Fresnel zone plates with spiral phase.

Focusing properties of Fresnel zone plates with spiral phase with integer and fractional topological charges illuminated by plane wave are studied. Numerical results show that hollow beams can be generated and can also be controlled by the number of the zones and the topological charge, which implies the potential applications of such kind of zone plate in trapping and manipulating particles.

Simultaneous monitoring of multiple urinary cytokines may predict renal and patient outcome in ischemic AKI.

Acute kidney injury (AKI) is a common disorder associated with high morbidity and mortality rates. Ischemia is the leading cause of AKI. This is a pilot study investigating the ability of multiple urinary cytokines to predict renal functional outcome and mortality in patients with ischemic AKI. Urine samples were obtained from 45 subjects with ischemic AKI on the day of renal consultation and 3 days later. The urinary concentrations of interleukin (IL)-1beta, IL-6, IL-8, monocyte chemotactic protein (MCP)-1, interferon-inducible protein (IP)-10, regulated on activation, normal T-expressed and secreted (RANTES), transforming growth factor (TGF)-alpha, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were measured simultaneously using a microsphere-based immunofluorescence assay. Urinary cytokine levels (pg/mg urine creatinine), which predict renal functional recovery or no recovery the next day and 7 days and 3 months later, were identified. Increased urinary IP-10 and IL-8 predicted no renal functional recovery the next day. Increased urinary IP-10 and VEGF predicted no renal recovery by 7 days. Increased urinary IP-10 and VEGF predicted no renal recovery by 4 days, whereas increased urinary EGF predicted renal functional recovery at that time. Increased urinary IL-8, MCP-1, IP-10, RANTES, EGF, and VEGF predicted patient's death within 3 months. Our findings suggest that urinary IP-10, IL-8, VEGF, TGF-alpha, and EGF may predict renal functional outcome at various times along the course of ischemic AKI and that urinary IL-8, MCP-1, IP-10, RANTES, EGF, and VEGF may predict mortality of the patients within 3 months.

Square Fresnel zone plate with spiral phase for generating zero axial irradiance.

A type of square Fresnel zone plate with spiral phase for generating zero axial irradiance is proposed. Diffraction patterns of the zone plates with different generalized topological charges are given by numerical simulation, which also suggests their potential applications in generating hollow beams.

TLR4 signaling mediates inflammation and tissue injury in nephrotoxicity.

The molecular mechanisms of acute kidney injury (AKI) remain unclear. Toll-like receptors (TLRs), widely expressed on leukocytes and kidney epithelial cells, regulate innate and adaptive immune responses. The present study examined the role of TLR signaling in cisplatin-induced AKI. Cisplatin-treated wild-type mice had significantly more renal dysfunction, histologic damage, and leukocytes infiltrating the kidney than similarly treated mice with a targeted deletion of TLR4 [Tlr4(-/-)]. Levels of cytokines in serum, kidney, and urine were increased significantly in cisplatin-treated wild-type mice compared with saline-treated wild-type mice and cisplatin-treated Tlr4(-/-) mice. Activation of JNK and p38, which was associated with cisplatin-induced renal injury in wild-type mice, was significantly blunted in Tlr4(-/-) mice. Using bone marrow chimeric mice, it was determined that renal parenchymal TLR4, rather than myeloid TLR4, mediated the nephrotoxic effects of cisplatin. Therefore, activation of TLR4 on renal parenchymal cells may activate p38 MAPK pathways, leading to increased production of inflammatory cytokines, such as TNF-alpha and subsequent kidney injury. Targeting the TLR4 signaling pathways may be a feasible therapeutic strategy to prevent cisplatin-induced AKI in humans.

Targeted disruption of the meprin metalloproteinase beta gene protects against renal ischemia-reperfusion injury in mice.

Meprins are membrane-bound and secreted metalloproteinases consisting of alpha- and/or beta-subunits that are highly expressed in mouse kidney proximal tubules. Previous studies have implied that the meprin alpha/beta-isoform is deleterious when renal tissue is subjected to ischemia-reperfusion (I/R). To delineate the roles of the meprin isoforms in renal disease, we subjected mice deficient in meprin-beta (KO) and their wild-type (WT) counterparts to I/R. WT mice were markedly more susceptible to renal injury after I/R than the meprin-beta KO mice as determined by blood urea nitrogen levels. Urinary levels of inflammatory cytokines IL-6 and KC (CXCL1) were significantly higher in WT compared with meprin-beta KO mice by 6 h post-I/R. At 96 h postischemia, kidney mRNA expression levels for tumor necrosis factor-alpha, transforming growth factor-beta, inducible nitric oxide synthase, and heat shock protein-27 were significantly higher in the WT than meprin-beta KO mice. For WT mice subjected to I/R, there was a rapid (3 h) redistribution of meprin beta-subunits in cells in S3 segments of proximal tubules, followed by shedding of apical cell membrane and detachment of cells. These studies indicate that meprin-beta is important in the pathogenesis of renal injury following I/R and that the redistribution of active meprin-alpha/beta is a major contributor to renal injury and subsequent inflammation.

Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice.

A major toxicity of the cancer chemotherapeutic agent cisplatin is acute renal failure. Sepsis is a common cause of acute renal failure in humans and patients who receive cisplatin are at increased risk for sepsis. Accordingly, this study examined the interactions between cisplatin and endotoxin in vivo with respect to renal function and cytokine production. Mice were treated with either a single dose of cisplatin or two doses of LPS administered 24 h apart, or both agents in combination. Administration of 10 mg/kg cisplatin had no effect on blood urea nitrogen or creatinine levels throughout the course of the study. LPS resulted in a modest rise in blood urea nitrogen at 24 and 48 h, which returned to normal by 72 h. In contrast, mice treated with both cisplatin and LPS developed severe renal failure and an increase in mortality. Urine, but not serum, TNF-alpha levels showed a synergistic increase by cisplatin and LPS. Urinary IL-6, MCP-1, KC, and GM-CSF also showed a synergistic increase with cisplatin+LPS treatment. The renal dysfunction induced by cisplatin+LPS was completely dependent on TLR4 signaling and partially dependent on TNF-alpha production. Increased cytokine production was associated with a moderate increase in infiltrating leukocytes which was not different between cisplatin+LPS and LPS alone. These results indicate that cisplatin and LPS act synergistically to produce nephrotoxicity which may involve proinflammatory cytokine production.

Dispersion phenomena demonstrated by a nanocarbon white point source.

Emission from nanocarbon as a point white-light source is studied in several scientific experiments, i.e., a demonstration of chromatic phenomena of a refractive lens, a diffractive Fresnel phase zone plate (FPZP), and a squared zone plate. Results show that white light from nanocarbon exhibits good coherent properties and can be an ideal point light source in comparison with other normal lighting sources, e.g., a light-emitting diode (LED), a He-Ne laser, and a semiconductor laser diode (LD). Dispersion and even diffraction phenomena could be analyzed this way as well.

Electromagnetic excitation of nano-carbon in vacuum.

Nano-carbon as lighting source is demonstrated in this paper. The characterized nano-radiation from nano-carbon, excited by different lasers in vacuum, is observed when laser intensity is over a threshold. With lower excitation threshold and smaller white light source, nano-carbon is more applicable to be as lighting system than the others in scientific experiments. White light emission of nano-carbon induced by more practicable electromagnetic excitation (microwave) is also demonstrated, which is caused by the faradic heating of the metal substrates, with molecular spectra and better color rendering. Lighting systems comprised of nano-carbon may become one of the considerable directions in optics.

Deletion of the mouse meprin beta metalloprotease gene diminishes the ability of leukocytes to disseminate through extracellular matrix.

Meprins are metalloendopeptidases expressed by leukocytes in the lamina propria of the human inflamed bowel, that degrade extracellular matrix proteins in vitro implicating them in leukocyte transmigration events. The aims of these studies were to 1) examine the expression of meprins in the mouse mesenteric lymph node, 2) determine whether macrophages express meprins, and 3) determine whether deletion of the meprin beta gene (Mep-1beta) mitigated the ability of leukocytes to disseminate through extracellular matrix in vitro. These studies show that meprin alpha and beta are expressed in leukocytes of the mouse mesenteric lymph node, and meprin alpha, but not beta, decreased during intestinal inflammation. Deletion of Mep-1beta gene decreased the ability of leukocytes to migrate through matrigel compared with wild-type leukocytes. Meprin beta, but not alpha, was detected in cortical and medullary macrophages of the lymph node. Thus overall, meprin beta is expressed by leukocytes in the draining lymph node of the intestine, regardless of the inflammatory status of the animal, and is likely to contribute to leukocyte transmigration events important to intestinal immune responses. Thus, the expression of meprins by leukocytes of the intestinal immune system may have important implications for diseases such as inflammatory bowel diseases, which are aggravated by leukocyte infiltration.