Novel glucomannan-like polysaccharide from Lycium barbarum L. ameliorates renal fibrosis via blocking macrophage-to-myofibroblasts transition.

The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-ß. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment.

Clinical Characteristics and Analysis of Associated Risk Factors in Patients with Severe and Non-Severe COVID-19 Infection.

Objective: Our aim was to highlight the clinical characteristics and determine the risk factors associated with severe and non-severe COVID-19 infection. Study Method: A retrospective review was conducted on clinical data obtained from patients with COVID-19 infection, admitted to the emergency department between November 2022 and January 2023. Total of 1684 participants were categorized into severe (312 cases,18.53%) and non-severe (1,372 cases,81.47%) cohorts. Logistic regression was utilized for multivariate analysis, with a P-value less than 0.05 signifying a significant difference between the groups. Results: The study consisted of 952 males (56.53%) and 732 females (43.47%) participants. The age distribution ranged from 18 to 93 years in both cohorts. There were statistically significant differences between the clinical symptoms of the severe and non-severe cohorts (P < 0.05). According to the multivariate statistical analysis, patients with more pronounced clinical manifestations had significantly elevated values related to age(P < 0.05), diabetes(P < 0.01), hypertension(P < 0.01), C-reactive protein (CRP) (P < 0.05), and lactate dehydrogenase (LDH) (P < 0.01) as compared to those presenting with milder symptoms. Conclusion: The primary clinical presentations in both the cohorts were mostly similar. Predominant factors contributing to the severity of COVID-19 infection were age, diabetes, hypertension, elevated CRP levels, and increased LDH.

Isolation, Purification, and Structural Characterization of Polysaccharides from Codonopsis pilosula and Their Anti-Tumor Bioactivity by Immunomodulation.

The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (<60 wDa), CPPS-II (60-100 wDa), and CPPS-III (>100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT-IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 µg/mL) group at 125 µg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

Rhodiola rosea polysaccharides-based nanoparticles loaded with DOX boosts chemo-immunotherapy for triple-negative breast cancer by re-educating Tumor-associated macrophages.

Hydrophobic drug delivery vectors suffer significant challenges in cancer therapy, including efficient encapsulation and tumor targeting ability. In the present study, Rhodiola rosea polysaccharides (RHPs), which have the ability to modulate Tumor-associated macrophages and typical structural characteristics, were employed as an immunoactive vector for drug delivery. Folic acid (FA) and stearic acid (SA) were chemically modified to the backbone of RHPs to obtain the self-assembly and tumor-targeting behavior. Further, the hydrophobic drug, doxorubicin (DOX), was encapsulated in the RHPs derivatives (FA-RHPs-SA) with high efficiency. Additionally, the optimally formed DOX@FA-RHPs-SA had a uniform size distribution of approximately 196 nm and a pH-sensitive release capacity in different acidic conditions. In vitro experiments demonstrated that tumor cells could efficiently uptake DOX@FA-RHPs-SA. Furthermore, the modulatory function of the FA-RHPs-SA on RAW264.7 macrophages was also demonstrated in the transition from M0 to M1 phenotypes, and the M2 differentiated into the M1. Finally, the in vivo antitumor study revealed that the inhibitory effect of DOX@FA-RHPs-SA was superior to the DOX monotherapy treatment, and the new preparation functioned synergistically by inducing tumor cell apoptosis and modulating immune cell function. In conclusion, this study described an RHPs-based hydrophobic delivery vector and achieved an additional helpful antitumor effect by modulating Tumor-associated macrophages.

Lung sound patterns help to distinguish congestive heart failure, chronic obstructive pulmonary disease, and asthma exacerbations.

OBJECTIVES: Although congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and asthma patients typically present with abnormal auscultatory findings on lung examination, respiratory sounds are not normally subjected to rigorous analysis. The aim of this study was to evaluate in detail the distribution of respiratory sound intensity in CHF, COPD, and asthma patients during acute exacerbation. METHODS: Respiratory sounds throughout the respiratory cycle were captured and displayed using an acoustic-based imaging technique. Breath sound distribution was mapped to create a gray-scale sequence of two-dimensional images based on intensity of sound (vibration). Consecutive CHF (n = 22), COPD (n = 19), and asthma (n = 18) patients were imaged at the time of presentation to the emergency department (ED). Twenty healthy subjects were also enrolled as a comparison group. Geographical area of the images and respiratory sound patterns were quantitatively analyzed. RESULTS: In healthy volunteers and COPD patients, the median (interquartile range [IQR]) geographical areas of the vibration energy images were similar, at 75.6 (IQR = 6.0) and 75.8 (IQR = 10.8) kilopixels, respectively (p > 0.05). Compared to healthy volunteers and COPD patients, areas for CHF and asthma patients were smaller, at 66.9 (IQR = 9.9) and 53.9 (IQR = 15.6) kilopixels, respectively (p < 0.05). The geographic area ratios between the left and right lungs for healthy volunteers and CHF and COPD patients were 1.0 (IQR = 0.2), 1.0 (IQR = 0.2), and 1.0 (IQR = 0.1), respectively. Compared to healthy volunteers, the geographic area ratio between the left and right lungs for asthma patients was 0.5 (IQR = 0.4; p < 0.05). In healthy volunteers and CHF patients, the ratios of vibration energy values at peak inspiration and expiration (peak I/E ratio) were 4.6 (IQR = 4.4) and 4.7 (IQR = 3.5). In marked contrast, the peak I/E ratios of COPD and asthma patients were 3.4 (= 2.1) and 0.1 (IQR = 0.3; p < 0.05), respectively. CONCLUSIONS: The pilot data generated in this study support the concept that relative differences in respiratory sound intensity may be useful in distinguishing acute dyspnea caused by CHF, COPD, or asthma.

Computerized lung sound analysis following clinical improvement of pulmonary edema due to congestive heart failure exacerbations.

BACKGROUND: Although acute congestive heart failure (CHF) patients typically present with abnormal auscultatory findings on lung examination, lung sounds are not normally subjected to rigorous analysis. The goals of this study were to use a computerized analytic acoustic tool to evaluate lung sound patterns in CHF patients during acute exacerbation and after clinical improvement and to compare CHF profiles with those of normal individuals. METHODS: Lung sounds throughout the respiratory cycle was captured using a computerized acoustic-based imaging technique. Thirty-two consecutive CHF patients were imaged at the time of presentation to the emergency department and after clinical improvement. Digital images were created, geographical area of the images and lung sound patterns were quantitatively analyzed. RESULTS: The geographical areas of the vibration energy image of acute CHF patients without and with radiographically evident pulmonary edema were (67.9 +/- 4.7) and (60.3 +/- 3.5) kilo-pixels, respectively (P < 0.05). In CHF patients without and with radiographically evident pulmonary edema (REPE), after clinical improvement the geographical area of vibration energy image of lung sound increased to (74.5 +/- 4.4) and (73.9 +/- 3.9) kilo-pixels (P < 0.05), respectively. Vibration energy decreased in CHF patients with REPE following clinical improvement by an average of (85 +/- 19)% (P < 0.01). CONCLUSIONS: With clinical improvement of acute CHF exacerbations, there was more homogenous distribution of lung vibration energy, as demonstrated by the increased geographical area of the vibration energy image. Lung sound analysis may be useful to track in acute CHF exacerbations.