The role of serum interleukins in Cancer: A Multi-center Mendelian Randomization study.

The occurrence of cancer is often accompanied by immune evasion and tumor-promoting inflammation, with interleukins (IL) playing a pivotal role in the immune-inflammatory mechanism. However, the precise contribution of serum interleukins in cancer remains elusive. We obtained GWAS summary data for 35 interleukins from eight independent large-scale serum proteome studies of European ancestry populations and for 23 common cancers from the FinnGen Consortium. We then conducted a multicenter Mendelian Randomization (MR) study to explore the relationship between systemic inflammatory status and cancers. 24 causal associations between interleukins and cancers were supported by multicenter data, 18 of which were reported for the first time. Our results indicated that IL-1α (Hodgkin lymphoma), IL-5 (bladder cancer), IL-7 (prostate cancer), IL-11 (bone malignant tumor), IL-16 (lung cancer), IL-17A (pancreatic cancer), IL-20 (bladder cancer), IL-22 (lymphocytic leukemia), IL-34 (breast cancer), IL-36ß (prostate cancer), and IL-36γ (liver cancer) were risk factors for related cancers. Conversely, IL-9 (malignant neoplasms of the corpus uteri), IL-17C (liver cancer), and IL-31 (colorectal cancer, bladder cancer, pancreatic cancer, and cutaneous melanoma) exhibited protective effects against related cancers. Notably, the dual effects of serum interleukins were also observed. IL-18 acted as a risk factor for prostate cancer, however, was a protective factor against laryngeal cancer. Similarly, IL-19 promoted the development of lung cancer and myeloid leukemia, while conferring protection against Breast, cervical, and thyroid cancers. Our study confirmed the genetic association between multiple serum interleukins and cancers. Immune and anti-inflammatory strategies targeting these associations provide opportunities for prevention and treatment.

Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis.

BACKGROUND: Spondyloarthritis (SpA) is a group of multifactorial bone diseases influenced by genetic factors, the environment and lifestyle. However, current studies have found a limited number of SpA-related genes, and the genetic and pathogenic mechanisms of SpA are still unclear. METHODS: A tissue-specific transcriptome-wide association study (TWAS) of SpA was performed using GWAS (including 3966 SpA patients and 448,298 controls) summary data and gene expression weights of whole blood and skeletal muscle. The SpA-associated genes identified by TWAS were further compared with the differentially expressed genes (DEGs) identified in the SpA gene expression profile acquired from the Gene Expression Omnibus database (GEO, GSE58667). Finally, functional enrichment and annotation analyses of the identified genes were performed. RESULTS: The TWAS detected 499 suggestive genes associated with SpA in whole blood and skeletal muscle, such as CTNNAL1 (PSM = 3.04 × 10-2, PWB = 9.58 × 10-3). The gene expression profile of SpA identified 20 candidate genes that overlapped in the TWAS data, such as MCM4 (PTWAS = 1.32 × 10-2, PDEG = 2.75 × 10-2) and KIAA1109 (PTWAS = 3.71 × 10-2, PDEG = 4.67 × 10-2). Enrichment analysis of the genes identified by TWAS identified 93 significant GO terms and 33 KEGG pathways, such as mitochondrion organization (GO: 0007005) and axon guidance (hsa04360). CONCLUSION: We identified multiple candidate genes that were genetically related to SpA. Our study may provide novel clues regarding the genetic mechanism, diagnosis, and treatment of SpA.

Polyphosphazene nanodrugs for targeting delivery and inflammation responsive release of curcumin to treat acute lung injury by effectively inhibiting cytokine storms.

An excessive inflammatory response induced by cytokine storms is the primary reason for the deterioration of patients with acute lung injury (ALI). Though natural polyphenols such as curcumin (CUR) have anti-inflammation activity for ALI treatment, they often have limited efficacy due to their poor solubility in water and oxidising tendency. This study investigates a highly cross-linked polyphosphazene nano-drug (PHCH) developed by copolymerisation of CUR and acid-sensitive units (4-hydroxy-benzoic acid (4-hydroxy-benzylidene)-hydrazide, D-HBD) with hexachlorotripolyphosphonitrile (HCCP) for improved treatment of ALI. PHCH can prolong the blood circulation time and targeted delivery into lung inflammation sites by enhancing CUR's water dispersion and anti-oxidant properties. PHCH also demonstrates the inflammation-responsive release of CUR in an inflammation environment due to the acid-responsive degradation of hydrazine bonds and triphosphonitrile rings in PHCH. Therefore, PHCH has a substantial anti-inflammation activity for ALI treatment by synergistically improving CUR's water-solubility, bioavailability and biocompatibility. As expected, PHCH attenuates the cytokine storm syndrome and alleviates inflammation in the infected cells and tissues by down-regulating several critical inflammatory cytokines (TNF-α, IL-1ß, and IL-8). PHCH also decreases the expression of p-p65 and C-Caspase-1, inhibiting NLRP3 inflammasomes and suppressing NF-κB signalling pathways. The administrated mice experiments confirmed that PHCH accumulation was enhanced in lung tissue and showed the efficient scavenging ability of reactive oxygen species (ROS), effectively blocking the cytokine storm and alleviating inflammatory damage in ALI. This smart polyphosphazene nano-drug with targeting delivery property and inflammation-responsive release of curcumin has excellent potential for the clinical treatment of various inflammatory diseases, including ALI.

Curcumin-Containing polyphosphazene nanodrug for Anti-Inflammation and nerve regeneration to improve functional recovery after spinal cord injury.

The microenvironment of excessive inflammation and the activation of apoptotic signals are primary barriers to neurological recovery following spinal cord injury (SCI). Thus, long-lasting anti-inflammation has become an effective strategy to navigate SCI. Herein, a curcumin (CUR)-containing nanosystem (FCTHPC) with high drug loading efficiency was reported via assembling hydrophobic CUR into cross-linked polyphosphazene (PPZ), and simultaneous loading and coordinating with porous bimetallic polymers for greatly enhanced the water-solubility and biocompatibility of CUR. The nanosystem is noncytotoxic when directing its biological activities. By inhibiting the expression of pro-inflammatory factors (IL-1ß, TNF-α and IL-6) and apoptotic proteins (C-caspase-3 and Bax/Bcl-2), which may be accomplished by activating the Wnt/ß-catenin pathway, the versatile FCTHPC can significantly alleviate the damage to tissues and cells caused by inflammation and apoptosis in the early stage of SCI. In addition, the long-term in vivo studies had demonstrated that FCTHPC could effectively inhibit the formation of glial scars, and simultaneously promote nerve regeneration and myelination, leading to significant recovery of spinal cord function. This study emphasises the promise of the biocompatible CUR-based nanosystem and provides a fresh approach to effectively treat SCI.

Brachial plexus injury after clavicle fracture operation: a case report and literature review.

BACKGROUND: Open reduction and internal fixation (ORIF) is the preferred choice for treating clavicle fractures. The brachial plexus injury caused by ORIF of a clavicle fracture is very rare. If it is not treated in time, the function of the brachial plexus will be challenging to recover, which will eventually lead to upper limb dysfunction and seriously affect the patient's quality of life. Our team recently used ORIF to treat a patient with a clavicle fracture, who developed brachial plexus injury symptoms after surgery. CASE PRESENTATION: A 34-year-old female patient was admitted to the hospital for 13 h due to the right shoulder movement restriction after a fall. Due to the significant displacement of the fracture, we used ORIF to treat the fracture. The surgery went well. When the anaesthesia effect subsided 12 h after the operation, the patient developed right brachial plexus injury symptoms, decreased right upper limb muscle strength, dysfunction, and hypoesthesia. Symptomatic treatments, such as nourishing nerve and electrical stimulation, were given immediately. Sixty days after the operation, the patient's brachial plexus injury symptoms disappeared, and the function of the right upper limb returned to the preoperative state. CONCLUSIONS: Patients with clavicle fractures usually need to undergo a careful physical examination before surgery to determine whether symptoms of brachial plexus injury have occurred. Anaesthesia puncture requires ultrasound guidance to avoid direct damage to the brachial plexus. When the fracture end is sharp, reset should be careful to prevent nerve stump stabbed. When using an electric drill to drill holes, a depth limiter should be installed in advance to prevent the drill from damaging the subclavian nerve and blood vessels. When measuring the screw depth, the measuring instrument should be close to the bone surface and sink slowly to avoid intense hooks and damage to the brachial plexus. Try to avoid unipolar electrosurgical units to prevent heat conduction from damaging nerves, and bipolar electrocoagulation should be used instead. If symptoms of brachial plexus injury occur after surgery, initial symptomatic treatment is drugs and functional exercise, and if necessary, perform surgical exploration.