Puerarin ameliorates metabolic dysfunction-associated fatty liver disease by inhibiting ferroptosis and inflammation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is frequently linked to type 2 diabetes mellitus (T2DM), and both conditions exacerbate the progression of the other. However, there is currently no standardized treatment or drug for MAFLD. In this study, A MAFLD animal model through a high-fat diet (HFD) along with administration of streptozotocin (STZ), and palmitic acid (PA)-induced AML12 cells were treated by puerarin. The objective of this study was to assess the therapeutic effect of puerarin, a flavonoid substance that possesses various pharmacological properties, on MAFLD. The results showed that puerarin administration enhanced glucose tolerance and insulin sensitivity, while also mitigating liver dysfunction and hyperlipidemia in MAFLD mice. Moreover, puerarin attenuated oxidative stress levels and inflammation in the liver. Transmission electron microscopy and Western blot analysis indicated that puerarin inhibited ferroptosis in vivo. Further mechanistic investigations revealed that puerarin upregulated SIRT1 expression, increased nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, and facilitated translocation into the nucleus. The protective effect of puerarin on PA-induced AML12 cells was diminished by the utilization of EX-527 (a SIRT1 inhibitor) and Nrf2 siRNA. Overall, the results demonstrate that puerarin ameliorates MAFLD by suppressing ferroptosis and inflammation via the SIRT1/Nrf2 signaling pathway. The results emphasize the possible medicinal application of puerarin for managing MAFLD.

Ultrasensitive Sandwich-Type SERS-Biosensor-Based Dual Plasmonic Superstructure for Detection of Tacrolimus in Patients.

Tacrolimus (FK506) is widely used in the prevention of organ transplant rejection and the treatment of autoimmune diseases, but it is difficult to detect within the low and narrow concentration range in practical clinical fields. A magnetic plasmonic superstructure-targets-plasmonic superstructure-based sandwich-type SERS biosensor is presented here to ultrasensitively detect FK506 in the blood of organ transplant patients. The spiky Fe3O4@SiO2@Ag flower magnetic superstructure and hollow Ag@Au superstructure enhanced the SERS signals by providing rich sharp tips, cavities, and abundant hot spot gaps. And the magnetic feature makes it easy to concentrate and separate the biological target. Using the designed sandwich-type SERS biosensor, FK506 could be detected within a range of 0.5-20 ng/mL with a detection limit of 0.33 ng/mL. All results indicated that the sandwich-type SERS biosensor has good stability, sensitivity, and anti-interference properties. It is noteworthy that this allowed us to successfully analyze FK506 in the blood of transplant patients, which is in strong agreement with the clinical results. Consequently, the attractive sandwich-type SERS biosensor can be used for the detection of FK506 in real samples, which is promising for clinical diagnosis.

Acidic oligosaccharide sugar chain combined with hyperbaric oxygen delays D-galactose-induced brain senescence in mice via attenuating oxidative stress and neuroinflammation.

Aging is fundamental to neurodegeneration and dementia. Preventing oxidative stress and neuroinflammation are potential methods of delaying the onset of aging-associated neurodegenerative diseases. The acidic oligosaccharide sugar chain (AOSC) and hyperbaric oxygen (HBO) can increase the expression of antioxidants and have a neuroprotective function. In this study, we investigate the ability of AOSC, HBO, and AOSC + HBO to prevent D-gal-induced brain senescence. The Morris water maze and Y-maze test results showed that all three therapies significantly attenuated D-gal-induced memory disorders. A potential mechanism of this action was decreasing elevated levels of oxidative stress and neuroinflammation. The western blot and morphological results showed that all three therapies decreased D-gal-induced neuroinflammation and downregulated inflammatory mediators including the nuclear factor κ-light-chain-enhancer of activated B cells, cyclooxygenase-2, interleukin-1ß, and tumor necrosis factor alpha. Taken together, our results indicated that AOSC, HBO, and AOSC + HBO therapies attenuated D-gal-induced brain aging in mice by repressing RAGE/NF-KB-induced inflammation, the activation of astrocytes and microglia, and a decrease in neuronal degeneration. These could be useful therapies for treating age-related neurodegenerative diseases such as Alzheimer's disease. Furthermore, HBO combined with AOSC had a better effect than HBO or AOSC alone.

Alginate Oligosaccharide Ameliorates D-Galactose-Induced Kidney Aging in Mice through Activation of the Nrf2 Signaling Pathway.

Aging is an independent risk factor for the development of age-related progressive kidney injury. As a part of the aging process, kidney aging has been indicated to be associated with oxidative stress-induced damage. Ameliorating oxidative damage is therefore considered a promising strategy for delaying kidney aging. Alginate oligosaccharide (AOS) has been reported to have a wide range of biological and pharmacological activities. However, no studies have focused on the role of AOS in delaying the kidney aging process. In this study, we aimed to evaluate the potential effects of AOS on kidney aging and its possible mechanisms. Subcutaneous injection of D-galactose (D-gal) (200 mg·kg-1·d-1) in C57BL/6J mice for 8 weeks was used to establish the aging model. AOS (200 mg·kg-1·d-1) was administered via oral gavage for the last four weeks. As a result, AOS inhibited the D-gal-induced upregulation of aging markers and significantly improved the kidney index and kidney function of D-gal-induced mice. In addition, AOS ameliorated the degree of tissue damage and fibrosis in the aging kidney. To further explore the potential mechanisms by which AOS attenuates the kidney aging process, the associated oxidative stress-induced damage was analyzed in depth. The data showed that AOS upregulated the expression of Klotho and decreased malondialdehyde levels by increasing the expression of antioxidant enzymes. Furthermore, our results suggested that AOS activated the nuclear factor erythrogen-2 associated factor 2 (Nrf2) pathway by promoting Nrf2 nuclear translocation in aging mice and upregulated the downstream expression of heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). In conclusion, the present study demonstrated that AOS is a promising agent for attenuating kidney aging, and the underlying molecular mechanisms are related to the activation of the Nrf2 signaling pathway.

BpForms and BcForms: a toolkit for concretely describing non-canonical polymers and complexes to facilitate global biochemical networks.

Non-canonical residues, caps, crosslinks, and nicks are important to many functions of DNAs, RNAs, proteins, and complexes. However, we do not fully understand how networks of such non-canonical macromolecules generate behavior. One barrier is our limited formats for describing macromolecules. To overcome this barrier, we develop BpForms and BcForms, a toolkit for representing the primary structure of macromolecules as combinations of residues, caps, crosslinks, and nicks. The toolkit can help omics researchers perform quality control and exchange information about macromolecules, help systems biologists assemble global models of cells that encompass processes such as post-translational modification, and help bioengineers design cells.

Expression of mutant CHMP2B linked to neurodegeneration in humans disrupts circadian rhythms in Drosophila.

Mutations in CHMP2B, an ESCRT-III (endosomal sorting complexes required for transport) component, are associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Neurodegenerative disorders including FTD are also associated with a disruption in circadian rhythms, but the mechanism underlying this defect is not well understood. Here, we ectopically expressed the human CHMP2B variant associated with FTD (CHMP2BIntron5) in flies using the GMR-GAL4 driver (GMR>CHMP2BIntron5) and analyzed their circadian rhythms at behavioral, cellular, and biochemical level. In GMR>CHMP2BIntron5 flies, we observed disrupted eclosion rhythms, shortened free-running circadian locomotor period, and reduced levels of timeless (tim) mRNA-a circadian pacemaker gene. We also observed that the GMR-GAL4 driver, primarily known for its expression in the retina, drives expression in a subset of tim expressing neurons in the optic lobe of the brain. The patterning of these GMR- and tim-positive neurons in the optic lobe, which appears distinct from the putative clusters of circadian pacemaker neurons in the fly brain, was disrupted in GMR>CHMP2BIntron5 flies. These results demonstrate that CHMP2BIntron5 can disrupt the normal function of the circadian clock in Drosophila.

Molecular Genetics of Frontotemporal Dementia Elucidated by Drosophila Models-Defects in Endosomal⁻Lysosomal Pathway.

Frontotemporal dementia (FTD) is the second most common senile neurodegenerative disease. FTD is a heterogeneous disease that can be classified into several subtypes. A mutation in CHMP2B locus (CHMP2Bintron5), which encodes a component of endosomal sorting complex required for transport-III (ESCRT-III), is associated with a rare hereditary subtype of FTD linked to chromosome 3 (FTD-3). ESCRT is involved in critical cellular processes such as multivesicular body (MVB) formation during endosomal⁻lysosomal pathway and autophagy. ESCRT mutants causes diverse physiological defects primarily due to accumulation of endosomes and defective MVBs resulting in misregulation of signaling pathways. Charged multivesicular body protein 2B (CHMP2B) is important for neuronal physiology which especially rely on precise regulation of protein homeostasis due to their post-mitotic status. Drosophila has proven to be an excellent model for charaterization of mechanistic underpinning of neurodegenerative disorders including FTD. In this review, current understanding of various FTD-related mutations is discussed with a focus on Drosophila models of CHMP2Bintron5-associated FTD.

[Effect of shallow needling combined with acupoint application on the acute stage of peripheral facial paralysis].

OBJECTIVE: To search for an effective therapy for the acute stage of peripheral facial paralysis. METHODS: One hundred and twenty cases of facial paralysis patients were randomly divided into an observation group and a control group, 60 cases in each group. Both groups were treated with routine medication, and the observation group was treated with shallow needling combined with acupoint application using self-made "acupoint application formula for facial paralysis" on the basis of the routine medication. The acupoints of Yifeng (TE 17), Wangu (GB 12), Dicang (ST 4), Jiache (ST 6), Yangbai (GB 14), Taiyang (EX-HN 5), Qianzheng (EX-HN 17), Cuanzhu (BL 2) in affected side and Hegu (LI 4) in healthy side were selected as main acupoints for shallow needling, and Qianzheng (EX-HN 17), Dicang (ST 4), Yangbai (GB 14) and Wangu (GB 12), or Jiache (ST 6), Taiyang (EX-HN 5), Quanliao (SI 18) and Yifeng (TE 17) were selected for acupoint application. The cure rate and the course of cured patients in both groups were compared. RESULTS: The cure rate of 88.3% (53/60) in observation group was superior to that of 66.7% (40/60) in control group (P < 0.01). The course of cured patients in observation group was obviously shorter than that of control group (P < 0.01). CONCLUSION: On the basis of routine medication, shallow needling combined with acupoint application can improve the therapeutic effect and shorten the course for acute stage of peripheral facial paralysis.