Research progress and application of liver organoids for disease modeling and regenerative therapy.

The liver is a major metabolic organ of the human body and has a high incidence of diseases. In recent years, the annual incidence of liver disease has increased, seriously endangering human life and health. The study of the occurrence and development mechanism of liver diseases, discovery of new therapeutic targets, and establishment of new methods of medical treatment are major issues related to the national economy and people's livelihood. The development of stable and effective research models is expected to provide new insights into the pathogenesis of liver diseases and the search for more effective treatment options. Organoid technology is a new in vitro culture system, and organoids constructed by human cells can simulate the morphological structure, gene expression, and glucose and lipid metabolism of organs in vivo, providing a new model for related research on liver diseases. This paper reviews the latest research progress on liver organoids from the establishment of cell sources and application of liver organoids and discusses their application potential in the field of liver disease research.

The Potential Mechanism of the Anti-Liver Fibrotic Effect of Curcumin in the Gut-Liver Axis.

This study aimed to explore the curative effect of curcumin on liver fibrosis and its correlation with the gut-liver axis in animal models. Histological staining was utilized to conduct histological analysis of the liver and intestine. An automatic biochemical analyzer or enzyme-linked immunosorbent assay system was utilized for analyzing the biochemical indexes in mice. Western blotting was employed to examine the level of relevant proteins. Furthermore, 16S rRNA high-throughput sequencing was performed to explore the impact of curcumin on intestinal microorganisms in rats with liver fibrosis. Ultrahigh-performance liquid chromatography with quadrupole-orbitrap mass spectrometry was utilized to analyze the effect of curcumin on rat feces metabolites. Our results showed that curcumin reduced the formation of collagen fibers caused by carbon tetrachloride in a dose-dependent manner. In addition, curcumin was able to restore intestinal permeability in rats with liver fibrosis. By adopting α diversity analysis (Chao 1 index, Shannon index, and Simpson index), we observed that both the diversity and the abundance of intestinal flora in rats with liver fibrosis were increased. The principal component analysis diagram demonstrated that curcumin could enhance the abundance and diversity of intestinal flora, and also restore the composition of model rat flora, which was similar to that in normal rats, thereby correcting the imbalance of flora in rats with liver fibrosis. In addition, curcumin regulated feces metabolites and their signaling pathways, including glycerophospholipid metabolism, pantothenate and CoA biosynthesis. Our findings suggest that curcumin exhibits antiliver fibrosis effects, and its antiliver fibrosis effects might correlate with gut-liver axis.

Hypofunction of macrophage chemotaxis contributes to defective efficacy of herceptin in HER2-positive breast cancer patients.

Breast cancer was considered as a kind of prone breast tumors with the complicated pathological mechanisms and diverse clinical classifications. In the clinical treatments of HER2-positive tumor patients, HER2 monoclonal antibodies, such as Herceptin, have shown well-defined therapeutic effects. Nevertheless, due to the heterogeneity of breast cancers, drug resistance inevitably appeared during the application of Herceptin. In order to fully understand the immune tolerance status of the tumor microenvironment in the population of sensitive and insensitive patients, this study carried out a series of studies through Luminex cytokines assay, clinicopathological analysis, immunofluorescence, and PCR. The results confirmed that in clinical samples sensitive to Herceptin, there were a large number of macrophages, and the protein expression levels and in situ expression of macrophage-related chemokines and inflammatory mediators are significantly higher than drug-resistant tumor samples. Further studies found that T cell function has a low correlation with tumor growth, and there are obvious obstacles in the process of peripheral blood immune cells entering the tumor microenvironment. In summary, this study provided clues for understanding the clinical drug resistance of HER2 monoclonal antibody and the clinical rational use of drugs and combination drugs.

HIG1 domain family member 1A is a crucial regulator of disorders associated with hypoxia.

Mitochondria play a central role in cellular energy conversion, metabolism, and cell proliferation. The regulation of mitochondrial function by HIGD1A, which is located on the inner membrane of the mitochondria, is essential to maintain cell survival under hypoxic conditions. In recent years, there have been shown other cellular pathways and mechanisms involving HIGD1A diametrically or through its interaction. As a novel regulator, HIGD1A maintains mitochondrial integrity and enhances cell viability under hypoxic conditions, increasing cell resistance to hypoxia. HIGD1A mainly targets cytochrome c oxidase by regulating downstream signaling pathways, which affects the ATP generation system and subsequently alters mitochondrial respiratory function. In addition, HIGD1A plays a dual role in cell survival in distinct degree hypoxia regions of the tumor. Under mild and moderate anoxic areas, HIGD1A acts as a positive regulator to promote cell growth. However, HIGD1A plays a role in inhibiting cell growth but retaining cellular activity under severe anoxic areas. We speculate that HIGD1A engages in tumor recurrence and drug resistance mechanisms. This review will focus on data concerning how HIGD1A regulates cell viability under hypoxic conditions. Therefore, HIGD1A could be a potential therapeutic target for hypoxia-related diseases.

miR-484: A Potential Biomarker in Health and Disease.

Disorders of miR-484 expression are observed in cancer, different diseases or pathological states. There is accumulating evidence that miR-484 plays an essential role in the development as well as the regression of different diseases, and miR-484 has been reported as a key regulator of common cancer and non-cancer diseases. The miR-484 targets that have effects on inflammation, apoptosis and mitochondrial function include SMAD7, Fis1, YAP1 and BCL2L13. For cancer, identified targets include VEGFB, VEGFR2, MAP2, MMP14, HNF1A, TUSC5 and KLF12. The effects of miR-484 on these targets have been documented separately. Moreover, miR-484 is typically described as an oncosuppressor, but this claim is simplistic and one-sided. This review will combine relevant basic and clinical studies to find that miR-484 promotes tumorigenesis and metastasis in liver, prostate and lung tissues. It will provide a basis for the possible mechanisms of miR-484 in early tumor diagnosis, prognosis determination, disease assessment, and as a potential therapeutic target for tumors.

Three-dimensional finite element analysis of cantilever fixed bridge supported by implants with mandibular central incisor / 中华口腔医学杂志

Objective@#To investigate effect of the contact surface between the bridge and the adjacent teeth on the stress distribution of the implant and bone tissue and the displacement of the prosthesis in the cantilever fixed implant bridge restoring missing mandibular central incisors.@*Methods@#Two-dimensional images of the mandible and dentition in healthy adults were obtained using CT data. A three-dimensional finite element model of cantilever fixed bridge supported by implants with mandibular central incisor was established by computer reconstruction technique.The contact surface between the bridge and the adjacent natural tooth was designed as "oval" and "trapezoid". The "trapezoid" has a slightly smaller median diameter on the labial side and a slightly larger medial diameter on the lingual side. Loading of 120 N was applied on the tangential margin of the middle line of the long axis of the bridge 41. The direction was set at 0°, which was parallel to the long axis of the tooth and downward. The buccal to lingual and downward angles were 30°, 45° and 60°, respectively, perpendicular to the long axis of the tooth and 90° to the lingual side.The stress distribution of the implant and surrounding bone tissue and the displacement of the prosthesis were compared between the two models.@*Results@#Under axial and buccolingual loading, the maximum equivalent stress peak in the implant and surrounding bone tissue in the cantilever with trapezoidal contact surface design and the maximum displacement of the prosthesis were lower. Moreover, the distribution of stress was more balanced and the concentration range of stress was smaller. With the loading angle increasing, this trend was more obvious. When loading angle increased to 90°, the maximum equivalent stress and the maximum displacement of the elliptic contact surface model implant and surrounding bone tissue were 196 and 101 MPa and 0.196 mm, respectively, while the trapezoidal contact surface model were 157 and 72 MPa and 0.164 mm, respectively.@*Conclusions@#The trapezoidal contact surface of the bridge and the adjacent teeth in the cantilever fixed bridge supported by implants with mandibular central incisor is beneficial to reduce the impact of the leverage on the implant and surrounding bone tissue.

Mechanical Dispersion of Nanoparticles and Its Effect on the Specific Heat Capacity of Impure Binary Nitrate Salt Mixtures.

In this study, the effect of nanoparticle concentration was tested for both CuO and TiO2 in eutectic mixture of sodium and potassium nitrate. Results showed an enhancement in specific heat capacity (Cp) for both types of nanoparticles (+10.48% at 440 °C for 0.1 wt % CuO and +4.95% at 440 °C for 0.5 wt % TiO2) but the behavior toward a rise in concentration was different with CuO displaying its highest enhancement at the lowest concentration whilst TiO2 showed no concentration dependence for three of the four different concentrations tested. The production of cluster of nanoparticles was visible in CuO but not in TiO2. This formation of nanostructure in molten salt might promote the enhancement in Cp. However, the size and shape of these structures will most likely impact the energy density of the molten salt.

Rheological Analysis of Binary Eutectic Mixture of Sodium and Potassium Nitrate and the Effect of Low Concentration CuO Nanoparticle Addition to Its Viscosity.

This paper is focused on the characterisation and demonstration of Newtonian behaviour of salt at both high and low shear rate for sodium and potassium nitrate eutectic mixture (60/40) ranging from 250 °C to 500 °C. Analysis of published and experimental data was carried out to correlate all the numbers into one meaningful 4th order polynomial equation. Addition of a low amount of copper oxide nanoparticles to the mixture increased viscosity of 5.0%-18.0% compared to the latter equation.

[Chief physician Lian Yu-lin's experience on treatment of cervical spondylosis by classification].

In clinical teaching practice of over 30 years, professor LIAN Yu-lin combines physiological, pathological and anatomic knowledge with TCM treatment based on syndrome differentiation, forming own unique theoretical system. This paper introduces LIAN's experience on treatment of cervical spondylosis in detail, and location of cervical vertebra three lines and determination of needling depth and reinforcing-reducing manipulation based on clinical manifestations of various types of cervical spondylosis, and combination of long needle with short needle, deep needling with superficially needling, stressing the main point and having a definite object. This is an effective pathway for treatment of cervical spondylosis.