Pterostilbene: a potential therapeutic agent for fibrotic diseases.

Fibrosis is a prevailing pathology in chronic diseases and accounts for 45% of deaths in developed countries. This condition is primarily identified by the transformation of fibroblasts into myofibroblasts and the overproduction of extracellular matrix (ECM) by myofibroblasts. Pterostilbene (PTS) is a natural analogue of resveratrol and is most commonly found in blueberries. Research has shown that PTS exerts a wide range of pharmacological effects, such as antioxidant, anti-inflammatory, and anticancer effects. As a result, PTS has the potential to prevent and cure numerous diseases. Emerging evidence has indicated that PTS can alleviate myocardial fibrosis, renal fibrosis, pulmonary fibrosis, hepatic fibrosis, and colon fibrosis via the inhibition of inflammation, oxidative stress, and fibrogenesis effects in vivo and in vitro, and the potential mechanisms are linked to various pathways, including transforming growth factor-ß1 (TGF-ß1)/small mother against decapentaplegic proteins (Smads) signalling, the reactive oxygen species (ROS)-driven Pitx2c/mir-15b pathway, nuclear factor kappa B (NF-κB) signalling, Kelch-like epichlorohydrin-associated protein-1 (Keap-1)/NF-E2-related factor-2 (Nrf2) cascade, the NLR family pyridine structure domain 3 (NLRP3) pathway, the Janus kinase-2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, and the Src/STAT3 pathway. In this review, we comprehensively summarize the antifibrotic effects of PTS both in vivo and in vitro and the pharmacological mechanisms, pharmacokinetics, and toxicology of PTS and provide insights into and strategies for exploring promising agents for the treatment of fibrosis.

The pharmacological role of Ginsenoside Rg3 in liver diseases: A review on molecular mechanisms.

Liver diseases are a significant global health burden and are among the most common diseases. Ginssennoside Rg3 (Rg3), which is one of the most abundant ginsenosides, has been found to have significant preventive and therapeutic effects against various types of diseases with minimal side effects. Numerous studies have demonstrated the significant preventive and therapeutic effects of Rg3 on various liver diseases such as viral hepatitis, acute liver injury, nonalcoholic liver diseases (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC). The underlying molecular mechanism behind these effects is attributed to apoptosis, autophagy, antioxidant, anti-inflammatory activities, and the regulation of multiple signaling pathways. This review provides a comprehensive description of the potential molecular mechanisms of Rg3 in the development of liver diseases. The article focuses on the regulation of apoptosis, oxidative stress, autophagy, inflammation, and other related factors. Additionally, the review discusses combination therapy and liver targeting strategy, which can accelerate the translation of Rg3 from bench to bedside. Overall, this article serves as a valuable reference for researchers and clinicians alike.

Targeting CDK4/6 in glioblastoma via in situ injection of a cellulose-based hydrogel.

Despite aggressive treatments, including surgery, chemotherapy and radiotherapy, the prognosis of glioblastoma (GBM) remains poor, and tumor recurrence is inevitable. The FDA-approved CDK4/6 inhibitor palbociclib (PB) showed interesting anti-GBM effects, but its brain penetration is limited by the blood-brain barrier. The aim of this project is to find whether the cellulose-based hydrogel via in situ injection could provide an alternative route to PB brain delivery and generate sufficient drug exposure in orthotopic GBM. In brief, PB was encapsulated in a cellulose nanocrystal network structure crosslinked by polydopamine via divalent Cu2+ and hexadecylamine. The formed hydrogel (PB@PH/Cu-CNCs) exhibited sustained drug retention and acid-responsive network de-polymerization for controlled release in vivo. Specifically, the released Cu2+ catalyzed a Fenton-like reaction to generate reactive oxygen species (ROS), which was further enhanced by PB, and consequently, irreversible senescence and apoptosis were induced in GBM cells. Finally, PB@PH/Cu-CNCs demonstrated a more potent anti-GBM effect than those treated with free PB or PH/Cu-CNCs (drug-free hydrogel) in cultured cells or in an orthotopic glioma model. These results prove that the injection of the PB-loaded hydrogel in situ is an effective strategy to deliver the CDK4/6 inhibitor into the brain and its anti-GBM effect can be further enhanced by combining Cu2+-mediated Fenton-like reaction.

Platycodin D represses ß-catenin to suppress metastasis of cetuximab-treated KRAS wild-type colorectal cancer cells.

Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, is extensively used for clinical therapy in KRAS wild-type colorectal cancer (CRC) patients. However, some patients still cannot get benefit from the therapy, because metastasis and resistance occur frequently after cetuximab treatment. New adjunctive therapy is urgently needed to suppress metastasis of cetuximab-treated CRC cells. In this study, we used two KRAS wild-type CRC cells, HT29 and CaCo2, to investigate whether platycodin D, a triterpenoid saponin isolated from Chinese medicinal herb Platycodon grandifloras, is able to suppress the metastasis of cetuximab-treated CRC. Label-free quantitative proteomics analyses showed that platycodin D but not cetuximab significantly inhibited expression of ß-catenin in both CRC cells, and suggested that platycodin D counteracted the inhibition effect of cetuximab on cell adherence and functioned in repressing cell migration and invasion. Western blot results showed that single platycodin D treatment or combined platycodin D and cetuximab enhanced inhibition effects on expressions of key genes in Wnt/ß-catenin signaling pathway, including ß-catenin, c-Myc, Cyclin D1 and MMP-7, compared to single cetuximab treatment. Scratch wound-healing and transwell assays showed that platycodin D combined with cetuximab suppressed migration and invasion of CRC cells, respectively. Pulmonary metastasis model of HT29 and CaCo2 in nu/nu nude mice consistently showed that combined treatment using platycodin D and cetuximab inhibited metastasis significantly in vivo. Our findings provide a potential strategy to inhibit CRC metastasis during cetuximab therapy by addition of platycodin D.

Identification of a Splicing Variant c.3813-3A>G in NPHP3 by Reanalysis of Whole Exome Sequencing in a Chinese Boy with Nephronophthisis.

Nephronophthisis is an autosomal recessive cystic kidney disease characterized by tubular injury and commonly results in kidney failure. We reported a case of 4-year-old Chinese boy presented with severe anemia, kidney, and liver dysfunction. Whole exome sequencing (WES) was performed to identify the candidate variant with a negative result initially. After complete collection of clinical information, reanalysis of WES identified a homozygous NPHP3 variant c.3813-3A>G (NM_153240.4). The effect on mRNA splicing of the intronic variant was predicted through software (three in silico splice tools). Furthermore, in vitro minigene assay was conducted to validate the predicted deleterious effects of the intronic variant. All of the splice prediction programs and minigene assay indicated that the variant had an impact on the normal splicing pattern of NPHP3. Our study confirmed the effect of the c.3813-3A>G variant on NPHP3 splicing in vitro, which gives additional evidence for the clinical significance of the variant and provides a basis for genetic diagnosis of nephronophthisis 3. In addition, we think that it is essential to reanalyze WES data after the complete clinical information collection to avoid missing some important candidate variants.

Astaxanthin: A promising therapeutic agent for organ fibrosis.

Fibrosis is the end-stage pathological manifestation of many chronic diseases. Infiltration of inflammatory cells and activation of myofibroblasts are the most prominent features of fibrosis, with excessive deposition of extracellular matrix (ECM) in tissues leading to organ tissue damage, which eventually progresses to organ failure and leads to high mortality rates. At present, a large number of studies have been conducted on tissue fibrosis, and the pathological mechanism of fibrosis development has generally been recognized. However, the prevention and treatment of fibrosis is still an unsolved problem, and a shortage of drugs that can be used in the clinic persists. Astaxanthin (ASTX), a carotenoid, is widely known for its strong antioxidant capacity. ASTX also has other biological properties, such as anti-inflammatory, antiaging and anticancer properties. Recently, many papers have reported that ASTX inhibits the occurrence and development of fibrosis by regulating signaling molecular pathways, such as transforming growth factor-ß/small mother against decapentaplegic protein (TGF-ß1/Smad), sirtuin 1 (SIRT1), nuclear factor kappa-B (NF-κB), microRNA, nuclear factor-E2-related factor 2/antioxidant response element (Nrf 2/ARE) and reactive oxygen species (ROS) pathways. By targeting these molecular signaling pathways, ASTX may become a potential drug for the treatment of fibrotic diseases. In this review, we summarize the therapeutic effects of ASTX on organ fibrosis and its underlying mechanisms of action. By reviewing the results from in vitro and in vivo studies, we analyzed the therapeutic prospects of ASTX for various fibrotic diseases and provided insights into and strategies for exploring new drugs for the treatment of fibrosis.

Effects of lower limb flexibility exercise on table tennis players physical fitness / Efeitos do exercício de flexibilidade dos membros inferiores sobre a aptidão física dos jogadores de tênis de mesa / Efectos del ejercicio de flexibilidad de las extremidades inferiores en la aptitud física de los jugadores de tenis de mesa

ABSTRACT Introduction: the main fitness requirements of table tennis players are highly automated motor skills and a strong body control ability; this combination is believed to benefit from flexibility exercises. Objective: Study the effects of lower limb flexibility training on physical fitness in table tennis players. Methods: The controlled experiment randomly divided 20 volunteers into two groups with no statistical differences between them. The control group continued using the existing table tennis teaching program, while the experimental group adopted the optimized lower limb flexibility training program. The course design was organized according to the physical education teacher's table tennis player talent training plan. Results: In the experimental group, the number of right body turns for throwing and blocking increased to 60.41 ± 4.67 times after the experiment; the number of right body turns increased to 64.045 ± 5.22; in the control group, the number of right push and blocks increased to 56.78 ± 3.67 times after the experiment. After the experiment, the number of fixed point swing speed of the whole station increased to 64.66 ± 3.95 (P<0.05). Conclusion: Adding lower limb flexibility exercises to table tennis flexibility training has been shown to improve athletes' static and dynamic flexibility, positively optimizing players' fitness. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: os principais requisitos de aptidão física dos jogadores de tênis de mesa são habilidades motoras altamente automatizadas e uma forte capacidade de controle corporal, acredita-se que essa combinação possa ser beneficiada com exercícios de flexibilidade. Objetivo: Estudar os efeitos do treinamento de flexibilidade dos membros inferiores sobre a aptidão física em jogadores de tênis de mesa. Métodos: O experimento controlado dividiu 20 voluntários, aleatoriamente, em dois grupos sem diferenças estatísticas entre si. O grupo de controle continuou a utilizar o programa de ensino do tênis de mesa existente, enquanto o grupo experimental adotou o programa de ensino de treinamento de flexibilidade dos membros inferiores otimizado. O projeto do curso foi organizado de acordo com o plano de treinamento de talentos de jogadores de tênis de mesa do professor de educação física. Resultados: No grupo experimental, o número de voltas à direita do corpo para arremesso e bloqueio aumentou para 60,41 ± 4,67 vezes após o experimento; o número de voltas à direita do corpo aumentou para 64,045 ± 5,22; no grupo de controle, o número de arremessos e bloqueios à direita aumentou para 56.78 ± 3.67 vezes após o experimento. Após o experimento, o número de velocidade de oscilação de ponto fixo de toda a estação aumentou para 64.66 ± 3.95 (P<0,05). Conclusão: Adicionar exercícios de flexibilidade dos membros inferiores ao treinamento de flexibilidade do tênis de mesa demonstrou melhorar a flexibilidade estática e dinâmica dos atletas, contribuindo positivamente para a otimização da aptidão física nos jogadores. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: los principales requisitos de aptitud física de los jugadores de tenis de mesa son unas habilidades motoras muy automatizadas y una gran capacidad de control corporal; se cree que esta combinación puede beneficiarse de los ejercicios de flexibilidad. Objetivo: Estudiar los efectos del entrenamiento de la flexibilidad de las extremidades inferiores en la aptitud física de los jugadores de tenis de mesa. Métodos: El experimento controlado dividió a 20 voluntarios, al azar, en dos grupos sin diferencias estadísticas entre ellos. El grupo de control siguió utilizando el programa de enseñanza de tenis de mesa existente, mientras que el grupo experimental adoptó el programa de enseñanza optimizado de entrenamiento de la flexibilidad de las extremidades inferiores. El diseño del curso se organizó de acuerdo con el plan de entrenamiento de talentos de jugadores de tenis de mesa del profesor de educación física. Resultados: En el grupo experimental, el número de giros del cuerpo derecho para lanzar y bloquear aumentó a 60,41 ± 4,67 veces después del experimento; el número de giros del cuerpo derecho aumentó a 64,045 ± 5,22; en el grupo de control, el número de empujes y bloqueos derechos aumentó a 56,78 ± 3,67 veces después del experimento. Después del experimento, el número de velocidad de swing de punto fijo de toda la estación aumentó a 64,66 ± 3,95 (P<0,05). Conclusión: Se ha demostrado que añadir ejercicios de flexibilidad de las extremidades inferiores al entrenamiento de flexibilidad del tenis de mesa mejora la flexibilidad estática y dinámica de los atletas, contribuyendo positivamente a la optimización de la aptitud física de los jugadores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

[Genetic analysis of two children with sporadic neurofibromatosis type 1 complicated with nephrotic syndrome].

OBJECTIVE: To explore the genetic basis for two children with sporadic neurofibromatosis type 1 (NF1) complicated with nephrotic syndrome (NS). METHODS: Clinical data of the children were collected. Both children were subjected to high-throughput sequencing, and candidate variants were verified by Sanger sequencing. RESULTS: Both children had café-au-lait macules, subaxillary freckle and Lisch nodules. Child 1 also had congenital tibiofibular pseudarthrosis on the left side. Genetic testing revealed that child 1 has harbored a heterozygous c.844C>T variant in the exon 8 of the NF1 gene, whilst child 2 has harbored a heterozygous c.1246C>T variant in the exon 11 of the NF1 gene. Both children were diagnosed with NF1 and have developed pronounced proteinuria, hypoalbuminemia, hypercholesterolemia and pitting edema at the ages of 3 and 10, respectively. Renal biopsy of child 2 has revealed minimal change nephropathy, and the diagnosis of nephrotic syndrome was established. Child 1 was treated with glucocorticoid, and child 2 was treated with glucocorticoid in combination with mycophenolate mofetil. The NS was relieved with no recurrence during 1 year's follow-up. CONCLUSION: NF1 combined with NS is rare in the clinical settings. The prognosis of children with NF1 combined with minimal change nephropathy is relatively good. Detection of NF1 gene variant can facilitate early identification and diagnosis of NF1.

Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma.

Hepatectomy is currently considered the most effective option for treating patients with early and intermediate hepatocellular carcinoma (HCC). Unfortunately, the postoperative prognosis of patients with HCC remains unsatisfactory, predominantly because of high postoperative metastasis and recurrence rates. Therefore, research on the molecular mechanisms of postoperative HCC metastasis and recurrence will help develop effective intervention measures to prevent or delay HCC metastasis and recurrence and to improve the long-term survival of HCC patients. Herein, we review the latest research progress on the molecular mechanisms underlying postoperative HCC metastasis and recurrence to lay a foundation for improving the understanding of HCC metastasis and recurrence and for developing more precise prevention and intervention strategies.

Young Patients With Colorectal Cancer Have Higher Early Mortality but Better Long-Term Survival.

INTRODUCTION: To define the prognosis of colorectal cancer (CRC) in young patients and to compare their postoperative treatment with that of older patients. METHODS: This multicenter study enrolled 5,457 patients with primary CRC who underwent surgical resection. The overall survival (OS), clinicopathologic characteristics, and postoperative treatment of 253 young patients aged 18-44 years and 5,204 older patients aged 44-80 years were analyzed. RESULTS: The OS rate was 77.1% for young and 74.2% for older patients (P = 0.348). Landmark analysis showed a significant difference in survival between young and older patients, with 63.8% of deaths among young patients being within 25 months of surgery compared with 42.4% among older patients (P = 0.002). Among those who survived more than 25 months, young patients had significantly better survival than older patients (P = 0.009). Multivariable analysis of young patients revealed that the tumor location, perineural invasion, and stage were associated with poor survival within 25 months; after this period, stage was the only prognostic marker. Young patients were more likely to receive chemotherapy, particularly multiagent regimens. For young patients, no significant difference in OS was found based on the chemotherapy regimen, regardless of disease stage (II, III, or IV, all P > 0.05). In addition, unlike in older patients, no difference in OS was found in young patients regardless of the drug regimen administered (all P > 0.05). DISCUSSION: Young-onset CRC may have a unique disease biology that warrants further research and therapy development.

The prognostic and clinical value of p53 upregulated modulator of apoptosis expression in solid tumors: a meta-analysis and TCGA data review.

BACKGROUND: Previous studies have reported the prognostic value of p53 upregulated modulator of apoptosis (PUMA) in numerous human tumors, but the conclusions have not been consistent. Therefore, this meta-analysis and the Cancer Genome Atlas (TCGA) data analysis were performed to estimate the prognostic significance of PUMA in solid tumors. RESEARCH DESIGN AND METHODS: A search was conducted in PubMed, Embase, Web of Science, Cochrane Library and CNKI up to 21 July 2022. In total, 10 studies with 2,207 patients were included. We extracted the overall survival (OS) and disease-free survival (DFS) data. The hazard ratios (HRs) and 95% confidence intervals (95% CI) were adopted for evaluating the association. RESULTS: Decreased PUMA expression was significantly associated with worse OS (HR = 0.54, 95% CI = 0.38-0.78) and worse DFS (HR = 0.54, 95% CI = 0.42-0.70). Subgroup analysis showed that the prognostic role of PUMA for OS was most significant in the digestive system (HR = 0.52, 95% CI = 0.38-0.69). Furthermore, the expression of PUMA was not affected by tumor differentiation or clinical stage, and TCGA dataset analysis confirmed these results. CONCLUSIONS: We proved that expression of PUMA may serve as an independent prognostic factor for patients with solid tumors.

Circular RNAs in hepatocellular carcinoma: Recent advances.

Circular RNAs (circRNAs) have covalently closed loop structures at both ends, exhibiting characteristics dissimilar to those of linear RNAs. Emerging evidence suggests that aberrantly expressed circRNAs play crucial roles in hepatocellular carcinoma (HCC) by affecting the proliferation, apoptosis and invasive capacity of HCC cells. Certain circRNAs may be used as biomarkers to diagnose and predict the prognosis of HCC. Therefore, circRNAs are expected to become novel biomarkers and therapeutic targets for HCC. Herein, we briefly review the characteristics and biological functions of circRNAs, focusing on their roles in HCC to provide new insights for the early diagnosis and targeted therapy of HCC.

Nitric oxide in multikinase inhibitor-induced hand-foot skin reaction.

Hand-foot skin reaction (HFSR) is the most debilitating and prevalent side effect caused by multikinase inhibitors (MKIs) that share vascular endothelial growth factor receptor (VEGFR) as the common inhibition target, such as sorafenib, regorafenib, axitinib, etc. Though not life-threatening, HFSR can significantly deteriorate patients' quality of life and jeopardize the continuity of cancer therapy. Despite years of efforts, there are no FDA-approved treatments for HFSR and the understanding of the precise pathogenic mechanism is still limited. In this study, we hypothesized that nitric oxide has the potential therapeutic effect to reverse the toxicity caused by MKI through upregulation of several VEGF/VEGFR downstream signaling pathways. We found that glyceryl trinitrate (GTN), a nitric oxide donor, could stimulate cell proliferation, migration, and protect cells from apoptosis induced by MKIs in vitro. Local application of GTN mitigated tissue damage in a rat model, while not impacting the anti-tumor effect of the MKI in HepG2 tumor-bearing mice. Finally, GTN ointment alleviated cutaneous damages and improved quality of life in 6 HFSR patients. Our study proposed and validated the mechanism to counteract VEGFR inhibition, providing GTN as the potential treatment to MKI-induced HFSR, which may further improve the therapeutic window of various MKI based cancer therapies.

Role of long noncoding RNA-mediated competing endogenous RNA regulatory network in hepatocellular carcinoma.

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are noncoding RNAs (ncRNAs) that occupy over 90% of the human genome, and their main function is to directly or indirectly regulate messenger RNA (mRNA) expression and participate in the tumorigenesis and progression of malignances. In particular, some lncRNAs can interact with miRNAs as competing endogenous RNAs (ceRNAs) to modulate mRNA expression. Accordingly, these RNA molecules are interrelated and coordinate to form a dynamic lncRNA-mediated ceRNA regulatory network. Mounting evidence has revealed that lncRNAs that act as ceRNAs are closely related to tumorigenesis. To date, numerous studies have established many different regulatory networks in hepatocellular carcinoma (HCC), and perturbations in these ceRNA interactions may result in the initiation and progression of HCC. Herein, we emphasize recent advances concerning the biological function of lncRNAs as ceRNAs in HCC, with the aim of elucidating the molecular mechanism underlying these HCC-related RNA molecules and providing novel insights into the diagnosis and treatment of HCC.

The combination of Biochanin A and SB590885 potentiates the inhibition of tumour progression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most aggressive and frequently diagnosed malignancy of the liver. Despite aggressive therapy, life expectancy of many patients in these cases is extended by only a few months. Hepatocellular carcinoma (HCC) has a particularly poor prognosis and would greatly benefit from more effective therapies. METHODS: The CCK-8 assay and colony formation assays were used to test the cell proliferation and viability. The effects of combination Biochanin A and SB590885 on apoptosis and cell cycle arrest of HCC cells were analysed by flow cytometry. The expression of ERK MAPK and PI3K/AKT/mTOR signalling as well as apoptosis and cell cycle-related proteins in HCC cells were tested by western blotting. The HCC cell xenograft model was established to test the tumor proliferation. Serum and plasma were tested for liver and kidney safety markers (ALP, ALT, AST, total bilirubin, creatinine, urea nitrogen) by using SpectraMax i3X. RESULTS: The combination of natural product Biochanin A with the BRAF inhibitor SB590885 synergistically suppressed proliferation, and promoted cell cycle arrest and apoptosis in vitro. Furthermore, we demonstrated that the combination of Biochanin A and SB590885 led to increased impairment of proliferation and HCC tumour inhibition through disrupting of the ERK MAPK and the PI3K/AKT pathways in vitro. The volumes tumors and the weights of tumours were significantly reduced by the combination treatment compared to the control or single treatments in vivo. In addition, we found that there was no significant hepatorenal toxicity with the drug combination, as indicated by the hepatorenal toxicity test. CONCLUSION: The results identify an effective combination therapy for the most aggressive form of HCC and provide the possibility of therapeutic improvement for patients with advanced HCC.

Resveratrol Sensitizes Colorectal Cancer Cells to Cetuximab by Connexin 43 Upregulation-Induced Akt Inhibition.

Cetuximab is a monoclonal antibody that acts as an anti-epidermal growth factor receptor (EGFR) agent. Cetuximab inhibits the phosphorylation and activation of EGFR and blocks downstream signal pathways of EGF/EGFR, including Ras-Raf-MAPK and PI3K-Akt pathways. Akt activation is an important factor in cetuximab resistance. It has been reported that resveratrol and connexin 43 regulate Akt in different ways based on tissue type. Since connexin 43 interacts with Akt, and resveratrol is known to upregulate connexin 43, we investigated whether resveratrol can sensitize colorectal cancer cells to cetuximab via connexin 43 upregulation. Our work confirmed that resveratrol increases the inhibition of growth by cetuximab in vitro and in vivo, upregulates connexin 43 expression and phosphorylation, increases gap junction function, and inhibits the activation of Akt and NFκB in parental or cetuximab-treated parental HCT116 and CT26 cells. Resveratrol did not exhibit these effects on connexin 43-shRNA transfected cells, so connexin 43 upregulation may contribute to Akt inhibition in these cells. Given these data, resveratrol may sensitize colorectal cancer cells to cetuximab via upregulating connexin 43 to inhibit the Akt pathway.

UV-responsive AKBA@ZnO nanoparticles potential for polymorphous light eruption protection and therapy.

Polymorphous light eruption (PLE) is one of the acquired idiopathic photodermatosis mainly induced by immoderate UV radiation. In order to realize UV protection and medicine administration simultaneously for polymorphous light eruption protection and therapy, Acetyl-11-keto-ß-boswellic acid (AKBA) loaded Zinc Oxide (ZnO) nanoparticles of which drug release behavior is UV-controlled has been successfully synthesized. Such nanoparticles can not only reflect UV but also transfer the energy to release AKBA which presents an excellent antioxidant and anti-inflammatory effects. In addition, they are biocompatible to HaCaT cells. As a result, they have a great potential in combining UV protection and medicine administration simultaneously for PLE protection and therapy.

A steroid-resistant nephrotic syndrome in an infant resulting from a consanguineous marriage with COQ2 and ARSB gene mutations: a case report.

BACKGROUND: Treatment of steroid-resistant nephrotic syndrome (SRNS) remains a challenge for paediatricians. SRNS accounts for 10~20% of childhood cases of nephrotic syndrome (NS). Individuals with SRNS overwhelmingly progress to chronic kidney disease (CKD) and end-stage kidney disease (ESRD). Genetic research is of great significance for diagnosis and treatment. More than 39 recessive or dominant genes have been found to cause human SRNS, including COQ2. COQ2 gene mutations not only cause primary coenzyme Q10 deficiency but also cause SRNS without extrarenal manifestations. The concept of COQ2 nephropathy has been proposed for a long time. Mutations in the COQ2 gene have rarely been reported. Worldwide, only 5 cases involving 4 families have been reported. CASE PRESENTATION: We present the case of a 6-month-old girl with steroid-resistant glomerulopathy due to a COQ2 defect with no additional systemic symptoms. The patient was identified as a homozygote for the c.832 T > C (p. Cys278Arg) missense mutation and a single base homozygous mutation in ARSB gene in c.1213 + 1G > A. The father and mother were heterozygous mutation carriers in both COQ2 and ARSB, and her healthy sister was only a heterozygous mutation carrier in COQ2. In this case, hormone therapy was ineffective, and progressive deterioration of renal function occurred within 1 week after onset, leading to acute renal failure and eventual death. CONCLUSIONS: We reported a consanguinity married family which had COQ2 and ARSB dual mutant. Kidney diseases caused by COQ2 gene mutations can manifest as SRNS, with poor prognosis. The C. 832 T > c (p.csc 278arg) is a new mutation site. Genetic assessment for children with steroid-resistant nephrotic syndrome, especially in infancy, is very important. Families with a clear family history should receive genetic counselling and prenatal examinations, and children without a family phenotype should also receive genetic screening as early as possible.

Synergistic activity of magnolin combined with B-RAF inhibitor SB590885 in hepatocellular carcinoma cells via targeting PI3K-AKT/mTOR and ERK MAPK pathway.

The prognosis of patients with advanced hepatocellular carcinoma (HCC) remains obscure. From a clinical point of view, the ERK MAPK pathway and the PI3K/AKT pathway are activated in the majority of liver cancer. In addition, long term used to single agent treatment of HCC, frequently results in reverse activation of the ERK MAPK pathway or the PI3K/AKT pathway, leading to drug resistance. Thus, it is important to research the mechanism of combination agents that could suppress different pathways to treat HCC. Here, we found that combination natural product magnolin with BRAF inhibitor SB590885 synergistically suppressed the proliferation, promoted cell cycle arrest and apoptosis in hepatocellular carcinoma cells Bel-7402 and SK-Hep1. Furthermore, we demonstrated that the magnolin and the SB590885 combination led to increased impaired proliferation via inhibition of the ERK MAPK pathway and the PI3K/AKT pathway. These findings highlight the important role of agent combination and provided the approaches of therapeutic improvement for patients with advanced HCC.

Role of the receptor tyrosine kinase Axl in hepatocellular carcinoma and its clinical relevance.

The receptor tyrosine kinase Axl and its ligand Gas6 regulate fundamental biological processes, including cell proliferation, survival and motility, through multiple downstream signaling pathways. Evidence to date suggests that aberrant Axl expression frequently occurs in many malignancies, including hepatocellular carcinoma, and that this is critical for promoting cell proliferation, migration, angiogenesis and metastasis. Moreover, deregulated Axl expression or activation is reportedly associated with resistance to cancer drugs and targeted cancer therapies. Thus, Axl inhibitors may represent a novel therapeutic approach for cancer treatment. This Review summarizes the latest advances concerning the biological role of Axl in hepatocellular carcinoma and its potential clinical relevance.