Serum Amyloid Research Articles

Specific plasma biomarker signatures associated with patients undergoing surgery for back pain

BACKGROUND CONTEXTIntervertebral disc degeneration (IDD) affects numerous people worldwide. The role of inflammation is increasingly recognized but remains incompletely resolved. Peripheral molecules could access neovascularized degenerated discs and contribute to the ongoing pathology. PURPOSETo assess a large array of plasma molecules in patients with IDD to identify biomarkers associated with specific spinal pathologies and prognostic biomarkers for the surgery outcome. DESIGNProspective observational study combining clinical data and plasma measures. PATIENT SAMPLEPlasma samples were collected just before surgery. Extensive clinical data (age, sex, smoking status, Modic score, glomerular filtration rate, etc.) were extracted from clinical files from 83 patients with IDD undergoing spine surgery. OUTCOME MEASURESRecovery 2 months postsurgery as assessed by the treating neurosurgeon. METHODSOver 40 biological molecules were measured in patients’ plasma using multiplex assays. Statistical analyses were performed to identify associations between biological and clinical characteristics (age, sex, Body Mass Index (BMI), smoking status, herniated disc, radiculopathy, myelopathy, stenosis, MODIC score, etc.) and plasma levels of biological molecules. RESULTSPlasma levels of Neurofilament Light chain (NfL) were significantly elevated in patients with myelopathy and spinal stenosis compared to herniated disc. Plasma levels of C- reactive protein (CRP), Neurofilament Light chain (NfL), and Serum Amyloid A (SAA) were negatively associated, while CCL22 levels were positively associated with an efficient recovery 2 months postsurgery. CONCLUSIONSOur results show that CRP and CCL22 plasma levels combined with the age of the IDD patient can predict the 2-month postsurgery recovery (Area Under the Curve [AUC]=0.883). Moreover, NfL could become a valuable monitoring tool for patients with spinal cord injuries.

Successfully treated refractory Sjögren’s syndrome myelopathy with tocilizumab; case report

Introduction and importance: myelitis in patients with Sjögren’s syndrome is rare and its incidence does not exceed 5%. It is usually treated with corticosteroids, immunosuppressants, and different treatment lines that have not yet been agreed upon. Case presentation: A 59-year-old man with a 10-year history of primary Sjögren’s syndrome (PSs) based on the presence of dry mouth and eyes, Schirmer’s test positivity, and anti-SS-A positivity. Suffering from about 3 months of history of weakness in the upper and lower extremities, about 3 months ago, Magnetic resonance imaging (MRI) consisting of cervical myelitis was performed. Because there was no other cause due to his previous Sjögren’s condition, Sjögren’s myelitis was considered a complication of PSs. He was placed on a treatment plan that included cyclophosphamide and corticosteroids, with good improvement clinically and radiologically on the MRI. Accordingly, he began gradually reducing the cortisone, but unfortunately, the patient relapsed and the symptoms worsened significantly, both clinically and on the MRI, before the patient entered the hospital. An increase in serum amyloid A protein (SAA) level was also found. Here, the treatment was moved to biological treatment. The patient was given subcutaneous tocilizumab (TCZ), 162 mg every 2 weeks, and the gradual improvement was good. No relapses occurred, and the level of SAA remained low until 8 months from the start of treatment. Corticosteroids were started to be reduced, and no relapses occurred in clinically and radiological symptoms. Discussion: We mentioned in this manuscript the case of a patient with PSs who had a complication of a neurological injury, namely cervical myelitis. He improved significantly on treatment with subcutaneous TCZ every 2 weeks, with complete remission of clinical and radiological symptoms and a decrease in the serum level of SAA, even after reducing the dose of cortisone without the risk of serious adverse events such as infections. Conclusion: In this case, subcutaneous TCZ has proven effective in treating myelitis when high protein amyloid A (SAA) levels are present in the blood. This may be the first case describing the effectiveness of TCZ in treating this condition.

A self-driven microfluidic immunosensor for rapid separation, enrichment, and detection of biomarkers in serum.

Biomarkers and their concentration levels are critical indicators of metabolomics for clinical applications. Rapid and sensitive analysis methods are essential for realizing timely and efficient quantitation of those significant biomarkers. In this work, a self-driven microfluidic immunosensor was developed for rapid all-in-one separation, enrichment, and detection of biomarkers. This immunosensor was constructed from a cyclic olefin copolymer (COC) channel layer and a polydimethylsiloxane (PDMS) sensing layer. The COC channel layer was modified through protein adsorption, immobilization, and remaining active site blocking. The obtained hydrophilic microchannels not only reduce the nonspecific adsorption, but also provide stable capillary-driven flow generation with linear velocities up to 20mm/s for aqueous solution auto-injection. The PDMS sensing layer was modified using capture antibodies to accomplish affinity recognition of target biomarkers. Procalcitonin (PCT) and serum amyloid A (SAA) were selected as model biomarkers in the feasibility study on applying the self-driven microfluidic immunosensor to bioassay. The limits of detection of PCT and SAA were 7.9ng/L and 7.6μg/L, respectively. Moreover, the whole process can be accomplished within 60min with excellent selectivity and reproducibility. In clinical serum sample analysis, satisfactory recoveries were achieved for PCT and SAA in the ranges of 85.0-103.0% and 95.5-106.0%, respectively, with relative standard deviations less than 5.3%. The method accuracy was further confirmed by the results of commercial immunoassay kits. This simple and easily operated immunosensor provides a rapid and sensitive biomarker analysis tool, and promotes the further development of automated and easy-to-use microfluidic immunoassays.

Associations of Neonatal Dairy Calf Faecal Microbiota with Inflammatory Markers and Future Performance.

After birth, the immune system is challenged by numerous elements of the extrauterine environment, reflected in fluctuations of inflammatory markers. The concentrations of these markers in the first month of life are associated with the future performance of dairy youngstock. It is thought that bacterial genera colonizing the calf intestinal tract can cause inflammation and thus affect their host's performance via immunomodulation. This study explored how the faecal microbiota of newborn dairy calves were related to inflammatory markers during the first three weeks of life, and if the abundance of specific genera was associated with first-lactation performance. Ninety-five female Holstein calves were studied. Once a week, serum and faecal samples were collected, serum concentrations of serum amyloid A, haptoglobin, tumour necrosis factor-α, and interleukin-6 were measured, and faecal microbiota composition was examined by 16S rRNA gene amplicon sequencing. Faecal Gallibacterium abundance in the first week of age and Collinsella abundance in the second week were negatively associated with inflammatory response as well as with calving-conception interval. Peptostreptococcus abundance in the second week of life was positively associated with inflammatory response and calving-conception interval, and negatively with average daily weight gain. In the third week, Dorea abundance was positively, Bilophila abundance was negatively associated with inflammatory response, and both genera were negatively associated with age at first calving. These bacterial genera may be able to influence the inflammatory response and through this, possibly the future performance of the dairy heifer. Deciphering such microbiota-host interactions can help improve calf management to benefit production and welfare.

Role of SAA1 in endometrial extracellular matrix remodeling in polycystic ovary syndrome: implication for pregnancy loss.

Abnormal endometrial extracellular matrix (ECM) remodeling compromises endometrial receptivity and diminishes the probability of a successful live birth. Serum amyloid A1 (SAA1), a modulator of inflammation, is elevated in the circulation of polycystic ovary syndrome (PCOS) patients and involved in ECM remodeling during tissue repair. However, the specific role of SAA1 in endometrial ECM remodeling and subsequent risk of pregnancy loss in PCOS patients remains unclear. To examine the role and underlying mechanism of SAA1 in ECM remodeling in the endometrium of PCOS patients. Serum samples from PCOS and control patients were utilized to investigate the relationship between the abundance of SAA1 and pregnancy loss. Human endometrial tissues and primary human endometrial stromal cells were used to examine the role and underlying mechanism of SAA1 in ECM remodeling. Serum SAA1 concentration was elevated and could serve as an independent risk of pregnancy loss in PCOS patients. Increased SAA1 abundance was also observed in endometrium obtained from these patients. Further mechanistic studies showed that SAA1 stimulated collagen I chains synthesis (COL1A1 and COL1A2) in endometrial stromal cells, suggesting excessive SAA1 may contribute to endometrial ECM remodeling, resulting in a non-supportive environment for ongoing pregnancy. This effect was abolished by either a toll-like receptors 2/4 antagonist or a nuclear factor κB inhibitor. The locally elevated levels of SAA1 in endometrium contribute to ECM over-deposition by inducing collagen I synthesis in PCOS patients, which may hamper embryo implantation and increase the risk of pregnancy loss. These observations highlight the crucial role of heightened SAA1 in orchestrating endometrial dysfunction and shed light on potential therapeutic avenues for improving reproductive outcomes in PCOS patients.

Acute phase reactants

The serum concentrations of certain proteins are altered in various conditions such as infection, trauma, inflammatory arthritis, malignancy, autoimmune and systemic inflammatory diseases. These proteins are known as positive or negative acute phase reactants. While albumin and transferrin belong to the negative acute phase reactants, alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-2-macroglobulin, C-reactive protein, ceruloplasmin, haptoglobin, serum amyloid A and fibrinogen are known as positive acute phase reactants. This review discusses the clinical use of C-reactive protein, erythrocyte sedimentation rate and procalcitonin.

BDMARD can prevent the progression of AA amyloidosis to end-stage renal disease

IntroductionAA amyloidosis (AA) can be the consequence of any chronic inflammatory disease. AA is associated with chronic inflammatory diseases (cid+AA), autoinflammatory syndromes (auto+AA) or AA of unknown origin or idiopathic...

Assessment of Serum Amyloid A in Healthy Children

Assessment of Serum Amyloid A in Healthy Children

Inflammation and Tumor Progression: The Differential Impact of SAA in Breast Cancer Models.

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model. Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice assessed with a multiplex assay, and tumor molecular biology and histology characterized with Western blotting and H&E histological staining. Results: WT tumor-bearing mice had increased levels of plasma SAA compared to wild-type control mice, while SAADKO control and tumor-bearing mice presented with lower levels of SAA in their plasma. SAADKO tumor-bearing mice also displayed significantly lower concentrations of systemic inflammatory markers. Tumors from SAADKO mice overall had lower levels of SAA compared to tumors from wild-type mice, decreased apoptosis and inflammasome signaling, and little to no tumor necrosis. Conclusions: We demonstrated that systemic SAA1/2 stimulates the activation of the NLRP3 inflammasome in breast tumors, leading to the production of pro-inflammatory cytokines. This, in turn, promoted apoptosis and tumor necrosis but did not significantly impact tumor growth or histological grading.

Development and application of a serious adverse events risk model for concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma.

The objective of this study was to construct a concise prediction model for serious adverse events (SAEs) in order to assess the likelihood of SAE occurrence among hospitalized patients undergoing concurrent chemoradiotherapy. An electronic database of a Cancer Centre was utilized to conduct a cross-sectional review survey. Our research involved the recruitment of 239 patients who were undergoing concurrent chemoradiotherapy in the Department of Nasopharynx and Radiotherapy. The clinical prediction rule was derived using logistic regression analysis, with SAE serving as the primary outcome. Internal verification was conducted. The occurrence rate of SAE in the derivation cohort was 59.4%. The ultimate model used had 3 variables, namely cystatin C, C-reactive protein, and serum amyloid A. The model exhibited an area under the curve of 0.626 (95% CI: 0.555-0.696; P < .001). The model accurately predicts the occurrence of SAE, and the variable data can be easily obtained, and the assessment technique is straightforward.

Cytokine and acute-phase proteins response following vaccination against infectious bronchitis in broilers.

Infectious bronchitis (IB) is an important disease of poultry, and vaccination is the best method of preventing IB in the poultry industry worldwide. This study was designed to evaluate cytokine and acute-phase protein (APP) responses and their correlations with antibody titres following vaccination regimes against IB in the broiler. Broilers were vaccinated with H120 and 1/96 vaccine strains, and MIX (H120+1/96) vaccine strains on Days 0 and 14. Heterophils/lymphocyte (H/L) ratio, APPs including chicken serum amyloid A (SAA), chicken pentraxin 3 (chPTX3), chicken interleukin 1β (IL-1β), chicken interleukin 6 (IL-6) levels and antibody titres were measured. An increase in the H/L ratio, SAA, chPTX3, IL-1β and IL-6 levels in vaccinated groups was observed 1 day after the first (highest rates) and second (lower levels) vaccination up to 3 days in three different patterns and then started to decrease. The results showed an immediate, short-lived response and moderate increases in all criteria. Changing patterns of APPs were different but in similar pattern after the first and second immunization in vaccinated groups. A positive correlation between all criteria values on Days 1 and 15 with antibody titres on Day 28 may indicate agonistic cross-regulation. Different types of IB vaccines could induce different patterns of APPs responses, which can be used to evaluate immune response outcomes in vaccine design, development and administration. The IL-6 with the highest increase can be a sensitive parameter and chPTX3 with the high increase could be an important criterion.

Diagnostic performance of liver stiffness as marker of liver involvement in systemic immunoglobulin light chain (AL) amyloidosis.

To investigate the diagnostic performance of liver stiffness for detecting liver involvement in immunoglobulin light chain (AL) amyloidosis. Liver stiffness was measured using transient elastography in 71 patients with systemic AL amyloidosis and 18 patients with wild type transthyretin (ATTRwt) amyloidosis with cardiomyopathy. Both non-invasive consensus criteria and serum amyloid P component (SAP) scintigraphy were used as substitute standards instead of liver biopsy for establishing liver involvement. Liver stiffness was higher in AL amyloidosis patients with liver involvement than in those without: this was observed using both consensus criteria (median 14.4kPa vs. 8.1kPa; p = 0.001) and SAP scintigraphy (median 20.9kPa vs. 6.2kPa; p < 0.001). Liver stiffness was also higher in AL amyloidosis patients with liver involvement compared to AL and ATTRwt amyloidosis patients with cardiac involvement. Based on receiver operating characteristic (ROC) curves a cut-off value of 14.4kPa for stiffness was optimal to indicate liver involvement, providing sensitivity and specificity of 50% and 74%, respectively, using the consensus criteria and 63% and 90%, respectively, using SAP scintigraphy as standard. Liver stiffness is a promising tool to establish liver involvement in AL amyloidosis having potential to become part of updated criteria for liver involvement.

Serum Amyloid P Secreted by Bone Marrow Adipocytes Drives Skeletal Amyloidosis.

The accumulation of amyloid fibrils has been identified in tissues outside the brain, yet little is understood about the formation of extracerebral amyloidosis and its impact on the aging process of these organs. Here, we demonstrate that both transgenic mice modeling Alzheimer's disease (AD) and naturally aging mice exhibit accumulated senescent bone marrow adipocytes (BMAds), accompanied by amyloid deposits surrounding the BMAds. Senescent BMAds acquire a secretory phenotype, resulting in a marked increase in the secretion of serum amyloid P component (SAP), also known as pentraxin 2 (PTX2). SAP/PTX2 colocalizes with amyloid deposits around senescent BMAds in vivo and is sufficient to promote the formation of insoluble amyloid deposits from soluble Aβ peptides in in vitro and ex vivo 3D BMAd-based culture experiments. Additionally, Combined treatment with SAP/PTX2 and Aβ peptides promotes osteoclastogenesis but inhibits osteoblastogenesis of the precursor cells. Transplantation of senescent BMAds into the bone marrow cavity of healthy young mice is sufficient to induce bone loss. Finally, pharmacological depletion of SAP/PTX2 from aged mice abolishes bone marrow amyloid deposition and effectively rescues the low bone mass phenotype. Thus, senescent BMAds, through the secretion of SAP/PTX2, contribute to the age-associated development of skeletal amyloidosis and resultant bone deficits.

Effects of Aureobasidium Pullulans produced β-1,3-1,6-glucan on CA19-9, sCD44, IgA and sCD209 in patients undergoing surgical resection of malignant pancreatic tumors.

96 Background: Pancreatic cancer is a highly refractory tumor with poor prognosis, which aggressively progresses by suppressing the immunity. Surgical procedure related stress further weakens the immunity and aids cancer stem cell metastases, warranting immune enhancement strategies. AFO-202 strain of Aureobasidium Pullulans produced β-1,3-1,6 glucan (Nichi BRITE), having yielded immune enhancement in earlier studies, we evaluated its effects in patients undergoing surgical resection of malignant pancreatic tumors. Methods: 30 subjects in two groups were enrolled; control arm (n=15, "P" group) received a placebo, and treatment arm (n=15, "G" group) received Nichi BRITE 250mg/day, in three divided doses, for 22 days from the pre-operative day. Serum beta glucan specific IgA2 (BG-IgA), total IgA (IgA), sCD209, Serum Amyloid A (SAA), sCD44 and CA19-9 were evaluated at base line and at periodic intervals. Results: sCD44 significantly decreased 48.94% in “G” group and only 4.58% in “P” group (p = &lt; 0.0001) on day 21. sCD209 on day 21 in “G” group increased by 54.68% (p = 0.04) against 15.03% in “P”. BG-IgA at day 10 increased around 150% in “G”, and only by 6% in “P”. Total IgA, increased by 20.60% in “G” and only 5.73% in “P”. SAA increased to 251.32% in “G” on day 21 and in “P” it decreased by 6.11%. Decreased sCD44 when correlated against Neutrophil to Lymphocyte Ratio (NLR), a significant positive correlation was in “G” (r statistic= 0.758; p-value =0.006; 95% CI= 0.2907~0.9335), but a negative correlation in “P”. Pancreatic cancer marker CA19-9 decreased significantly in three months follow up in “G” (-86.02 U/ml) whereas it increased in “P” by +5.91 U/ml. Mean survival of Nichi BRITE group was 25.9 months against 22.3 months in “P” group. Conclusions: Administration of Nichi BRITE glucans to patients undergoing surgical resection of malignant pancreatic tumor was safe and it enhanced biomarkers of innate and adaptive immunity. Nichi BRITE significantly decreased the circulating cancer stem cell marker sCD44 implying a lesser recurrence risk, especially in patients with high NLR ratio who have a poor prognosis, and significantly reduced the CA 19-9 levels implying a better prognosis, making us recommend it as an adjuvant to patients undergoing surgeries for malignant tumors, and be included in the guidelines of clinical nutrition.

Prognostic value and therapeutic response of neutrophil-to-lymphocyte ratio in penile cancer.

116 Background: Chronic inflammation mediated by poor genital hygiene is a well-recognized pathogenic trigger for penile squamous cell carcinoma (PSCC). The neutrophil-to-lymphocyte ratio (NLR) is a simple and reproducible factor reflecting the systemic inflammatory response and has been reported as an unfavorable indicator in PSCC. However, previous studies limited by small sample sizes, confounding prognostic features and without high-quality evidence to demonstrate the clinical significance of the NLR. Methods: A large cohort of 582 penile cancer patients who underwent radical inguinal lymphadenectomy with definitive pN stages were enrolled in this study. Univariate and multivariate Cox regression analyses were performed to investigate prognostic factors and inflammation-related markers in PSCC patients. More importantly, the propensity score matching (PSM) method was used to minimize the prognostic confounding clinicopathological features. Immunofluorescence was further used to investigate the correlation between tumor-infiltrating neutrophils, CD8+ T cells and the NLR. Results: According to the ROC curve, the optimal cutoff value for the NLR was 3.0, and 226 (38.8%) PSCC patients had a high NLR. Survival analyses indicated that advanced pT, pN, pathological grade, lymphovascular invasion, high NLR, C-reactive protein (≥ 2.2 mg/L) and serum amyloid A (≥ 11.3 mg/L) were associated with poor PFS and CSS. After PSM to eliminate interference from clinical factors, pN and the NLR were found to be independent prognostic indicators in PSCC patients (both p&lt;0.001). Cox multivariate regression analysis revealed that the HR for PFS was 1.64 (1.15–2.34) in the high NLR group and 1.56 (1.04–2.34) in the high NLR group (p=0.006 and 0.030, respectively). PSCC patients with high NLRs experienced shorter PFS after receiving cisplatin-based chemotherapy (p=0.037) and PD-1 immunotherapy (p=0.020). In addition, we found that the infiltration of tumor-associated neutrophils (CD66+) and the CD8+ T-cell ratio were positively correlated with the NLR. The development and formation of neutrophil extracellular traps (NETs) might contribute to chemoresistance and tumor progression in high-NLR PSCC patients. Conclusions: In this study, we demonstrated that the NLR is an effective, simple and independent prognostic indicator for PSCC. The NLR holds promise as a powerful tool to guide decision-making in clinical practice. [Table: see text]

Immune and inflammation features of severe and critical Omicron infected patients during Omicron wave in China

ObjectiveThe current study aimed to investigate the baseline immune and inflammatory features and in-hospital outcomes of patients infected with the Omicron variant (PIWO) who presented with different disease severities during the first wave of mass Omicron infections in the Chinese population has occurred.MethodA cross‐sectional study was conducted on 140 hospitalized PIWO between December 11, 2022, and February 16, 2023. The clinical features, antibodies against SARS-CoV-2, immune cells, and inflammatory cytokines among mildly, severely, and critically ill PIWO at baseline and during follow-up period were compared.ResultPatients with severe (n = 49) and critical (n = 35) disease were primarily male, needed invasive mechanical ventilation treatment, and exhibited higher mortality than those with mild disease (n = 56). During acute infection, SARS-CoV-2-specific antibody levels fluctuated with disease severity, serum antibodies increased and the incidence of severe cases decreased in critically ill PIWO over time. Antibody titers in severe or critical PIWO with no antibody responses at baseline did not increase significantly over time. Meanwhile, CD4+T cell, CD8+T cell, and natural killer cell counts were negatively correlated with disease severity, whereas interleukin (IL)-6 and IL-10 levels were positively correlated. In addition, combined diabetes, immunosuppressive therapy before infection, serum amyloid A, IL-10 and neutrophil counts were independently associated with severe and critical illness in PIWO. Among the 11 nonsurvivors, 8, 2, 1 died of respiratory failure, sudden cardiac death, and renal failure, respectively. Compared with survivors, nonsurvivors exhibited lower seropositivity of SARS-CoV-2-specific antibody, reduced CD3+T and CD4+T cell counts, and higher IL-2R, IL-6, IL-8, and IL-10 levels. Of note, lactate dehydrogenase was a significant risk factor of death in severe or critically ill PIWO.ConclusionThis present study assessed the dynamic changes of SARS-CoV-2-specific antibodies, immune cells and inflammatory indexes between severely and critically ill PIWO. Critical and dead PIWO featured compromised humoral immune response and excessive inflammation, which broadened the understanding of the pathophysiology of Omicron infection and provides warning markers for severe disease and poor prognosis.

Proteomic Profiling of HDL in Newly Diagnosed Breast Cancer Based on Tumor Molecular Classification and Clinical Stage of Disease.

The association between high-density lipoprotein (HDL) cholesterol and breast cancer (BC) remains controversial due to the high complexity of the HDL particle and its functionality. The HDL proteome was determined in newly diagnosed BC classified according to the molecular type [luminal A or B (LA or LB), HER2, and triple-negative (TN)] and clinical stage of the disease. Women (n = 141) aged between 18 and 80 years with BC, treatment-naïve, and healthy women [n = 103; control group (CT)], matched by age and body mass index, were included. Data-independent acquisition (DIA) proteomics was performed in isolated HDL (D = 1.063-1.21 g/mL). Results: Paraoxonase1, carnosine dipeptidase1, immunoglobulin mMu heavy chain constant region (IGHM), apoA-4, and transthyretin were reduced, and serum amyloid A2 and tetranectin were higher in BC compared to CT. In TNBC, apoA-1, apoA-2, apoC-2, and apoC-4 were reduced compared to LA, LB, and HER2, and apoA-4 compared to LA and HER2. ComplementC3, lambda immunoglobulin2/3, serpin3, IGHM, complement9, alpha2 lysine rich-glycoprotein1, and complement4B were higher in TNBC in comparison to all other types; complement factor B and vitamin D-binding protein were in contrast to LA and HER2, and plasminogen compared to LA and LB. In grouped stages III + IV, tetranectin and alpha2-macroglobulin were reduced, and haptoglobin-related protein; lecithin cholesterol acyltransferase, serum amyloid A1, and IGHM were increased compared to stages I + II. Conclusions: A differential proteomic profile of HDL in BC based on tumor molecular classification and the clinical stage of the disease may contribute to a better understanding of the association of HDL with BC pathophysiology, treatment, and outcomes.

DaiTongXiao improves gout nephropathy by inhibiting inflammatory response through the TLR4/MyD88/NF-κB pathway.

Introduction: Gouty nephropathy (GN) arises from factors like excessive purine intake, metabolic disorders or abnormal synthesis, and uric acid hypersaturation in the blood, leading to urate crystal deposition in kidney tissue. DaiTongXiao (DTX) is a remedy used by the Dai people of China. It shows efficacy in lowering uric acid levels and exhibits anti-inflammatory and kidney-protective properties. Methods: A GN rat model was induced using adenine and potassium oxonate. Following DTX administration, various parameters were assessed in urine, serum, and kidney tissue. Western blot analysis evaluated TLR4/MyD88/NF-κB signaling proteins, while immunofluorescence examined NF-κB nuclear expression. Results: DTX treatment improved kidney morphology, increased body weight, and kidney index and enhanced urinary levels of blood urea nitrogen (Bun), 24-h urinary protein, uric acid (UA), and allantoin in GN rats, reducing UA, Bun, creatinine (Cre), cystatin C (CysC), serum amyloid A (SAA), α1-microglobulin (MG), and β2-MG in serum analysis. Renal tissue assessments showed decreased xanthine oxidase (XOD), hydroxyproline (Hyp), α-smooth muscle actin (α-SMA), and collage type Ⅳ (COL-Ⅳ). Kidney damage severity was notably reduced. DTX lowered serum inflammatory factors like interleukin (IL) -18, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), transforming growth factor-β1 (TGF-β1), and IL-1β in the rat serum, reducing chemokine monocyte chemoattractant protein-1 (MCP-1) and adhesion factor vascular cell adhesion molecule-1(VCAM-1). Western blotting demonstrated the downregulation of TLR4/MyD88/NF-κB pathway proteins, and immunofluorescence revealed reduced NF-κB expression in renal tissue. Discussion: DTX exhibits significant anti-GN effects by modulating TLR4/MyD88/ NF-κB pathway protein expression, reducing inflammatory factor release, and inhibiting GN progression.

Key charged residues influence the amyloidogenic propensity of the helix-1 region of serum amyloid A

Increased plasma levels of serum amyloid A (SAA), an acute-phase protein that is secreted in response to inflammation, may lead to the accumulation of amyloid in various organs thereby obstructing their functions. Severe cases can lead to a systemic disorder called AA amyloidosis. Previous studies suggest that the N-terminal helix is the most amyloidogenic region of SAA. Moreover, computational studies implicated a significant role for Arg-1 and the residue-specific interactions formed during the fibrillization process. With a focus on the N-terminal region of helix-1, SAA1–13, mutational analysis was employed to interrogate the roles of the amino acid residues, Arg-1, Ser-5, Glu-9, and Asp-12. The truncated SAA1–13 fragment was systematically modified by substituting the key residues with alanine or uncharged but structurally similar amino acids. We monitored the changes in the amyloidogenic propensities, associated conformational markers, and morphology of the amyloids resulting from the mutation of SAA1–13. Mutating out Arg-1 resulted in much reduced aggregation propensity and a lack of detectable β-structures alluding to the importance of salt-bridge interactions involving Arg-1. Our data revealed that by systematically mutating the key amino acid residues, we can modulate the amyloidogenic propensity and alter the time-dependent conformational variation of the peptide. When the behaviors of each mutant peptide were analyzed, they provided evidence consistent with the aggregation pathway predicted by MD simulation studies. Here, we detail the important temporal molecular interactions formed by Arg-1 with Ser-5, Glu-9, and Asp-12 and discuss its mechanistic implications on the self-assembly of the helix-1 region of SAA.

Correlations between Immunoinflammatory Factor Levels and Cognitive Functions and Brain Structural Magnetic Resonance Imaging Features among Patients with Primary Schizophrenia.

Schizophrenia is associated with significant cognitive impairment. However, the pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. Based on the latest concept of cognition, immunoinflammatory factors and structural magnetic resonance imaging (sMRI) features of the brain are considered markers of schizophrenia. This study explored the correlations between cognitive function and immunoinflammatory factors and sMRI in primary schizophrenia patients. Non-interventional cross-sectional study was conducted, including 21 patients with primary schizophrenia, who were identified based on the Diagnostic and Statistical Manual, Fifth Edition (DSM-V) and grouped under the observation group. Thirty healthy volunteers with age, gender, hand dominance, and education duration matched with those of the primary schizophrenia patients were recruited to the control group. All subjects underwent sMRI examination. MATRICS consensus cognitive battery (MCCB) was employed to assess the cognitive functions among patients with primary schizophrenia. The levels of serum amyloid A (SAA), monocyte chemoattractant protein 1 (MCP-1), and chitinase-3-like protein 1 (YKL-40) were measured by means of enzyme-linked immunosorbent assay (ELISA). Pearson's correlation analysis was carried out to analyze the correlation between immunoinflammatory factor levels and cognitive functions as well as brain sMRI features. The scores for all MCCB items and the total score for the observation group were apparently lower than those for the control group (p < 0.001), while the YKL-40 and SAA levels were notably higher in the observation group (t = 3.406, p < 0.05; t = 5.656, p < 0.001). Compared to the control group, the observation group exhibited reduced volumes of left and right insular lobes, left and right anterior cingulate cortexes, left and right hippocampi, right parahippocampal gyrus, right amygdala, left inferior occipital lobe, left superior temporal lobe, left temporal pole, and left middle and inferior temporal lobes (p < 0.001). The levels of YKL-40 and SAA were both negatively correlated with MCCB score (r = -0.3668, p = 0.004; r = -0.8495, p < 0.001). The volumes of right insular lobe, left and right anterior cingulate cortexes, right parahippocampal gyrus, right amygdala, and gray matter in left middle temporal lobe were all negatively correlated with the levels of YKL-40 and SAA (p < 0.05). Cognitive impairment in patients with primary schizophrenia is associated with increased serum SAA and YKL-40 levels and decreased gray matter volume.