Peptides derived from growth factors: Exploring their diverse impact from antimicrobial properties to neuroprotection.

Growth factor-derived peptides are bioactive molecules that play a crucial role in various physiological processes within the human body. Over the years, extensive research has revealed their diverse applications, ranging from antimicrobial properties to their potential in neuroprotection and treating various diseases. These peptides exhibit innate immune responses and have been found to possess potent antimicrobial properties against a wide range of pathogens. Growth factor-derived peptides have demonstrated the ability to promote neuronal survival, prevent cell death, and stimulate neural regeneration. As a result, they hold immense promise in the treatment of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, as well as in the management of traumatic brain injuries. Moreover, growth factor-derived peptides have shown potential for supporting tissue repair and wound healing processes. By enhancing cell proliferation and migration, these peptides contribute to the regeneration of damaged tissues and promote a more efficient healing response. The applications of growth factor-derived peptides extend beyond their therapeutic potential in health; they also have a role in various disease conditions. For example, researchers have explored their influence on cancer cells, where some peptides have demonstrated anti-cancer properties, inhibiting tumor growth and promoting apoptosis in cancer cells. Additionally, their immunomodulatory properties have been investigated for potential applications in autoimmune disorders. Despite the immense promise shown by growth factor-derived peptides, some challenges need to be addressed. Nevertheless, ongoing research and advancements in biotechnology offer promising avenues to overcome these obstacles. The review summarizes the foundational biology of growth factors and the intricate signaling pathways in various physiological processes as well as diseases such as cancer, neurodegenerative disorders, cardiovascular ailments, and metabolic syndromes.

Comparison of the Global Leadership Initiative on Malnutrition and the Patient-Generated Subjective Global Assessment for diagnosing malnutrition in patients undergoing surgery for hepatobiliary and pancreatic malignancies.

OBJECTIVE: to analyse the differences in malnutrition assessment between the Global Leadership Initiative on Malnutrition (GLIM) criteria and the Patient-Generated Subjective Global Assessment (PG-SGA) among patients with hepatobiliary and pancreatic malignancies. METHOD: this study was a cross-sectional study and included 126 hospitalised patients who underwent surgery for hepatobiliary and pancreatic malignancies between November 1, 2019 and August 1, 2020. The patients' clinical data were collected, and malnutrition assessments were completed using the different nutritional assessment tools. The consistency of both tools was analysed using Cohen's kappa coefficient. RESULTS: the prevalence of malnutrition showed a difference in diagnosis results between the GLIM criteria (36.51 %) and the PG-SGA (55.56 %). The two methods had moderate consistency (kappa = 0.590, p < 0.01). The sensitivity of a malnutrition diagnosis using a combination of GLIM and PG-SGA was 65.7 % (53.3 % and 76.4 %, respectively), and specificity was 100 % (92 % and 100 %, respectively). When malnutrition was evaluated using only PG-SGA, sensitivity was 88.9 % (95 % confidence interval (CI) 63.9 % to 98.1 %), whereas when only the GLIM score was used for malnutrition evaluation, sensitivity was 98.2 % (95 % CI, 92.8 % to 99.7 %). In addition, the PG-SGA score and the GLIM score had significant correlations. CONCLUSION: GLIM performed better than PG-SGA in the correlation analysis of nutritional indicators. GLIM is more suitable for patients with hepatobiliary and pancreatic malignancies than PG-SGA.

Deep learning-assisted ultrasonic diagnosis of cervical lymph node metastasis of thyroid cancer: a retrospective study of 3059 patients.

Objective: This study aimed to develop a deep learning system to identify and differentiate the metastatic cervical lymph nodes (CLNs) of thyroid cancer. Methods: From January 2014 to December 2020, 3059 consecutive patients with suspected with metastatic CLNs of thyroid cancer were retrospectively enrolled in this study. All CLNs were confirmed by fine needle aspiration. The patients were randomly divided into the training (1228 benign and 1284 metastatic CLNs) and test (307 benign and 240 metastatic CLNs) groups. Grayscale ultrasonic images were used to develop and test the performance of the Y-Net deep learning model. We used the Y-Net network model to segment and differentiate the lymph nodes. The Dice coefficient was used to evaluate the segmentation efficiency. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the classification efficiency. Results: In the test set, the median Dice coefficient was 0.832. The sensitivity, specificity, accuracy, PPV, and NPV were 57.25%, 87.08%, 72.03%, 81.87%, and 66.67%, respectively. We also used the Y-Net classified branch to evaluate the classification efficiency of the LNs ultrasonic images. The classification branch model had sensitivity, specificity, accuracy, PPV, and NPV of 84.78%, 80.23%, 82.45%, 79.35%, and 85.61%, respectively. For the original ultrasonic reports, the sensitivity, specificity, accuracy, PPV, and NPV were 95.14%, 34.3%, 64.66%, 59.02%, 87.71%, respectively. The Y-Net model yielded better accuracy than the original ultrasonic reports. Conclusion: The Y-Net model can be useful in assisting sonographers to improve the accuracy of the classification of ultrasound images of metastatic CLNs.

A protocol for the stereoselective synthesis of a Star of David [2]catenane.

Most complex prime links exhibit inherent topological chirality, yet their high stereoinduction remains a rare occurrence. Here, we present a protocol for the stereoselective synthesis of a molecular link comprising two triple entwined rings. We describe steps for constructing the precursor circular helicate, performing ring closure metathesis, and demetallation. We also outline procedures for bio-beads separation and data analysis. This protocol holds promise for applications in molecular nanotopology. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).1.

Syndrome of liver depression and spleen deficiency is a primary TCM syndrome of response to entecavir + FuZheng HuaYu in patients with HBV-related liver fibrosis.

Objective: Although clinical studies have found that Chinese patent medicine FuZheng HuaYu tablet/capsule can promote the reversal of HBV-related liver fibrosis, not all sufferers have histopathological responses. This study aims to explore the correlation between traditional Chinese medicine (TCM) syndromes and response to entecavir + FuZheng HuaYu (ETV + FZHY) in patients with HBV-related liver fibrosis. Methods: This a multi-center cross-sectional study. According to the different treatment strategies that sufferers have ever received, a total of 437 cases were included and divided into ETV + FZHY group and ETV + placebo group. And based on the relevant efficacy determination criteria, the two groups were subdivided into efficacy responders and non-responders. Then, TCM clinical questionnaire information of these patients were collected for subsequent analysis to acquire relevant syndrome elements and TCM syndromes. Results: No matter what group was, the first three frequency of TCM pathological position in efficacy responders were as follows: Liver > Spleen > Stomach (TCM concepts). As for the ETV + FZHY group, the first three frequency of pathological nature was ranked as Qi deficiency > Dampness > Heat. Compared with the non-responders, the frequency of Spleen, Stomach, Qi deficiency, Heat, and Qi movement stagnation was significantly increased in the efficacy responders (P < 0.05). In terms of TCM syndromes, the frequency increase of Syndrome of liver depression and spleen deficiency (LDSD), in the efficacy responders, changed more obviously than the non-responders (Chi2 = 6.32, P = 0.0006). Conclusions: TCM syndrome elements of Spleen, Stomach, Qi deficiency, Heat, and Qi movement stagnation were closely associated with efficacy responders with HBV-related liver fibrosis in the ETV + FZHY group. Moreover, LDSD was a primary TCM syndrome in these responders.

Practical semi-quantum key distribution with one-way key and one basis.

Semi-quantum key distribution (SQKD) protocols are used to distribute secret keys between a quantum party and a classical party. However, existing SQKD protocols rely on two-way communication, and may still be vulnerable to Trojan horse side-channel attacks where Eve sends her own photon into a receiver's apparatus and measures the reflected photon to estimate the key. In this paper, we propose a practical SQKD with one-way key. This requires that the single photons travelling through the one-way channel are used to encode bit information, and the returned photons are used to quantify Eve's information, thus reducing the security analysis of the Trojan horse attack in SQKD. Meanwhile, our protocol with one basis enjoys security advantage in practical SQKD systems when source flaws are taken into account. In particular, the present protocol is secure under practical conditions when weak coherent pulses (WCP) are used. Our simulation results show that the protocol using WCP can distribute secret keys over a distance of 110 km without decoy states.

Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet.

BACKGROUND: After receiving entecavir or combined with FuzhengHuayu tablet (FZHY) treatment, some sufferers with hepatitis B virus (HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen. Serum metabolomics at baseline in these patients who were effective in treatment remain unclear. AIM: To explore baseline serum metabolites characteristics in responders. METHODS: A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited. First, all subjects were divided into training set and validation set. Second, the included patients were subdivided into entecavir responders (E-R), entecavir no-responders (E-N), FZHY + entecavir responders (F-R), and FZHY + entecavir no-responders (F-N) following the pathological histological changes after 48 wk' treatments. Then, Serum samples of all subjects before treatment were tested by high performance liquid chromatography-tandem mass spectrometry (LC-MS) high-performance LC-MS. Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis. Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression. RESULTS: As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N, results showed that 4 pathways including linoleic acid metabolism, aminoacyl-tRNA biosynthesis, cyanoamino acid metabolism, alanine, aspartate and glutamate metabolism were screened out. As for the differential metabolites, these 7 intersected metabolites including hydroxypropionic acid, tyrosine, citric acid, taurochenodeoxycholic acid, benzoic acid, 2-Furoic acid, and propionic acid were selected. CONCLUSION: Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Squamous cell carcinoma of the cystic duct: A case report and literature review.

RATIONALE: Pure squamous cell carcinoma (SCC) of the gallbladder is a rare malignant biliary tract tumor predominantly found in the body and neck of the gallbladder. However, its occurrence in the cystic duct is even rarer. Given its rarity, no established guidelines or consensus currently exist regarding the treatment of pure SCC of the gallbladder. We report an unusual case of SCC originating from the cystic duct with the intent of providing insights into the therapeutic approach for this type of malignancy. PATIENT CONCERNS: A male patient presented to our hospital with acute cholecystitis. Unexpectedly, imaging revealed gallbladder malignancy. DIAGNOSES: Pathologic examination after surgery confirmed SCC of the cystic duct. INTERVENTIONS: Despite elevated bilirubin levels, we were able to exclude hilar involvement, enabling radical tumor resection. Intraoperatively, we discovered that the tumor was located in the cystic duct, a site associated with a high likelihood of invasion into neighboring organs. The tumor demonstrated a predominantly exophytic growth pattern, which prompted us to refrain from extending the resection range, thereby striking a balance between complete tumor removal and surgical trauma. We performed liver wedge resection only to ensure a negative resection margin while preserving the anatomical structure to the greatest extent possible. Postoperative recovery was rapid and uncomplicated. Pathological examination confirmed pure SCC, which led us to initiate a regimen of nab-paclitaxel and cisplatin, which is known to be effective in other organ SCCs. Remarkably, the patient experienced a rare and severe posttreatment cardiovascular event. Consequently, we switched the patient to a chemotherapy regimen of gemcitabine and cisplatin, which ultimately yielded positive clinical outcomes. OUTCOMES: no evidence of tumor recurrence was observed within 1 year after surgery. LESSONS: The diagnosis and therapeutic strategy for rare tumors such as gallbladder SCC should be meticulously tailored based on their unique characteristics to optimize postoperative patient outcomes.

A new isoflavone from the stems of Derris eriocarpa How.

A preliminary screening test was performed to discover new antihyperlipidaemic active compounds from the leguminous plant Derris eriocarpa How. A new compound, derris-isoflavone F (1), and derrubone dimethyl ether (6), a known synthetic compound of natural origin, were isolated from the stems of D. eriocarpa alongside eight recognised compounds. To our knowledge, this is the first instance of documenting the identification of compounds 1-10 from this plant. The new compound were evaluated for their antihyperlipidemic and antiproliferative properties. Compound 1 evidently reduced the triglyceride (TG) content in oleic acid-treated HepG2 cells, which validated its efficacy as a potential TG-lowering agent.

Gold Nanobipyramid Hotspot Aggregation-Induced Surface-Enhanced Raman Scattering for the Ultrasensitive Detection of miRNA.

Herein, a surface-enhanced Raman scattering (SERS) biosensor was constructed by gold nanobipyramid (Au NBP) hotspot aggregation-induced SERS (HAI-SERS) for the ultrasensitive detection of microRNA-221 (miRNA-221). Impressively, compared with single Au NBP, the multiple Au NBPs assembled by tetrahedral DNA nanostructures (TDNs) could increase hotspot aggregation to significantly enhance the SERS signal of Raman molecule methylene blue (MB). Meanwhile, in the aid of Exo-III assisted target cycle amplification and TDNs-induced catalytic hairpin assembly (CHA) amplification, the biosensor could achieve the sensitive detection of miRNA-221 with a linear range of 1 fM-10 nM, and the limit of detection (LOD) was 0.59 fM, which could be used for practical application in MHCC-97L and MCF-7 cell lysates. This work provided a method for hotspot aggregation to enhance SERS for the detection of biomarkers and disease diagnosis.

Pteryxin suppresses osteoclastogenesis and prevents bone loss via inhibiting the MAPK/Ca2+ signaling pathways mediated by ROS.

Osteoporosis, as a severe public health problem worldwide, causes systemic damage to bone mass, strength, and microstructure with an increased propensity for fragility fractures. Given the inherent adverse effects associated with long-term use of current prescription medications for osteoporosis treatment, identifying natural alternatives to existing treatment methods is imperative. Pteryxin (PTX), a natural coumarin, is isolated from the Peucedanum species belonging to the family Apiaceae. PTX has been reported to have antioxidant, anti-inflammatory and anti-obesity properties. However, its effect on osteoporosis has not been clarified. Our study confirmed that PTX could attenuate the formation of osteoclasts and bone resorption on a dose-dependent basis in vitro. Consistently, in vivo ovariectomy (OVX)-induced osteoporosis models simulating the physiological characteristics of postmenopausal women showed that PTX could partially reverse the bone loss caused by OVX. Further study of its mechanism revealed that PTX might block the MAPK and Ca2+-calcineurin-NFATc1 signaling pathways by decreasing the reactive oxygen species (ROS) level in osteoclasts to dampen the expression of critical transcriptional NFATc1 and downstream osteoclast-specific genes. Overall, PTX may present a new or alternative treatment option for osteoporosis.

Machine learning algorithms assist early evaluation of enteral nutrition in ICU patients.

Background: This study applied machine learning (ML) algorithms to construct a model for predicting EN initiation for patients in the intensive care unit (ICU) and identifying populations in need of EN at an early stage. Methods: This study collected patient information from the Medical Information Mart for Intensive Care IV database. All patients enrolled were split randomly into a training set and a validation set. Six ML models were established to evaluate the initiation of EN, and the best model was determined according to the area under curve (AUC) and accuracy. The best model was interpreted using the Local Interpretable Model-Agnostic Explanations (LIME) algorithm and SHapley Additive exPlanation (SHAP) values. Results: A total of 53,150 patients participated in the study. They were divided into a training set (42,520, 80%) and a validation set (10,630, 20%). In the validation set, XGBoost had the optimal prediction performance with an AUC of 0.895. The SHAP values revealed that sepsis, sequential organ failure assessment score, and acute kidney injury were the three most important factors affecting EN initiation. The individualized forecasts were displayed using the LIME algorithm. Conclusion: The XGBoost model was established and validated for early prediction of EN initiation in ICU patients.

Noise effective masking level for bone conduction of wide-spectrum short-duration signals in normal hearing adults.

OBJECTIVE: The objective of this study is to determine the noise effective masking level (EML) and inter-aural attenuation (IA) for click and CE-Chirp signals presented though a Radioear B-81 to elicit the auditory brainstem responses in normally hearing, young adults. DESIGN AND STUDY SAMPLE: A total of 26 conveniently sampled adults (13 male and 13 female, aged 18-25 years; 52 ears), with pure-tone hearing thresholds not >15 dB nHL at octave frequencies from 250 to 8000 Hz, and subjective thresholds for the bone-conducted click and CE-Chirp not >10 dB nHL. RESULTS: At stimulus intensities of 30 and 40 dB nHL, the contralateral EML was 67.86 ± 0.78 and 77.80 ± 0.81 dB SPL (respectively) for the click and 72.11 ± 0.74 and 83.53 ± 0.78 dB SPL (respectively) for the CE-Chirp. At stimulus intensities of 30 and 40 dB nHL, the IA was 3.46 ± 2.34 and 3.38 ± 2.03 dB (respectively) for both the click and the CE-Chirp. CONCLUSION: EML and IA values are reported for click and CE-Chirp signals presented at 30 and 40 dB nHL though a Radioear B-81 to elicit the ABR in normally hearing, young adults.

Biological valorization of lignin to flavonoids.

Lignin is the most affluent natural aromatic biopolymer on the earth, which is the promising renewable source for valuable products to promote the sustainability of biorefinery. Flavonoids are a class of plant polyphenolic secondary metabolites containing the benzene ring structure with various biological activities, which are largely applied in health food, pharmaceutical, and medical fields. Due to the aromatic similarity, microbial conversion of lignin derived aromatics to flavonoids could facilitate flavonoid biosynthesis and promote the lignin valorization. This review thereby prospects a novel valorization route of lignin to high-value natural products and demonstrates the potential advantages of microbial bioconversion of lignin to flavonoids. The biodegradation of lignin polymers is summarized to identify aromatic monomers as momentous precursors for flavonoid synthesis. The biosynthesis pathways of flavonoids in both plants and strains are introduced and compared. After that, the key branch points and important intermediates are clearly discussed in the biosynthesis pathways of flavonoids. Moreover, the most significant enzyme reactions including Claisen condensation, cyclization and hydroxylation are demonstrated in the biosynthesis pathways of flavonoids. Finally, current challenges and potential future strategies are also discussed for transforming lignin into various flavonoids. The holistic microbial conversion routes of lignin to flavonoids could make a sustainable production of flavonoids and improve the feasibility of lignin valorization.

Pharmacology-based molecular docking of 4-methylcatechol and its role in RANKL-mediated ROS/Keap1/Nrf2 signalling axis and osteoclastogenesis.

4-Methylcatechol (4-MC) is an agonist of various neurotrophic factors, which can upregulate the expression of Heme oxygenase 1 (HO-1) protein by activating nuclear factor erythroid 2-related factor 2 (Nrf2), thereby inhibiting oxidative stress-induced neural stem cell death. During RANKL-stimulated osteoclast differentiation, intracellular reactive oxygen species (ROS) levels were increased. Nonetheless, the effect of 4-MC on osteoclast formation and bone resorption function has not been researched. In this study, we investigated the effect of HO-1 upregulation by 4-MC on RANKL-induced osteoclastogenesis and explored the molecular mechanism of HO-1 upregulation by 4-MC. We found that the small molecule compound 4-MC could bind to Keap1 amino acid residue of glycine GLY 367, isoleucine ILE 559 and valine VAL 606, with a predicted binding energy of -4.99 kcal/mol. 4-MC was found to inhibit osteoclast differentiation in vitro by activating Nrf2 to scavenge ROS, inhibiting NF-κB phosphorylation, and alleviating osteoporosis in ovariectomized (OVX) mice. Taken together, 4-MC reduces ROS by inhibiting Keap1, thereby preventing OVX-induced bone loss.

Corylifol A protects against ovariectomized-induced bone loss and attenuates RANKL-induced osteoclastogenesis via ROS reduction, ERK inhibition, and NFATc1 activation.

Osteoclast differentiation and function are critical targets for anti-osteoporosis treatment. Oxidative stress also plays an important regulatory role in the differentiation of osteoclasts. Corylifol A (CA) is a flavonoid extracted from the Psoralea fruit. It has anti-inflammatory and antioxidant properties despite its unknown effect on osteoporosis. This study found that CA prevented estrogen-deficiency-induced bone loss and suppressed osteoclastogenesis in ovariectomized (OVX) mice by inhibiting intracellular reactive oxygen species (ROS) levels. In vivo, CA effectively prevented trabecular bone loss and reduced osteoclasts' number on the bone surface in OVX mice, as demonstrated in micro-CT, osteometry, and immunohistochemical data. However, CA did not affect cortical bone. In vitro, CA inhibited RANKL-induced podosome belt formation, osteoclastogenesis, and bone resorption functions. CA suppressed RANKL-induced ROS by boosting antioxidant enzymes (Catalase and NQO1) and NFATc1 signaling pathway related protein expression, including integrin αvß3, NFATc1 and CTSK. Moreover, CA inhibited osteoclast-specific genes, including Ctsk, Acp5, and Mmp9. CA also attenuated the MAPK/ERK pathway, but did not affect the NF-κB signaling pathway. In terms of osteogenesis, CA did not inhibit or promote osteogenic differentiation and mineralization in vitro. These results reveal that CA could be a new replacement therapy for treating estrogen-deficiency osteoporosis via suppressing osteoclastogenesis and intracellular ROS.

Effects of Nintedanib associated with Shenfu Injection on paraquat-induced lung injury in rats / 中华劳动卫生职业病杂志

Objective: To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat (PQ) intoxication. Methods: In September 2021, a total of 90 SD rats were divided into 5 groups in random, namely control group, PQ poisoning group, Shenfu Injection group, Nintedanib group and associated group, 18 rats in each group. Normal saline was given by gavage route to rats of control group, 20% PQ (80 mg/kg) was administered by gavage route to rats of other four groups. 6 hours after PQ gavage, Shenfu Injection group (12 ml/kg Shenfu Injection), Nintedanib group (60 mg/kg Nintedanib) and associated group (12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib) were administered with medicine once a day. The levels of serum transforming growth factor beta1 (TGF-β1), interleukin-1 beta (IL-1β) were determined at 1, 3 and 7 d, respectively. The pathological changes of lung tissue, the ratio of wet weight and dry weight (W/D) of lung tissue, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were observed and determined after 7 d. Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1 (FGFR1), platelet derivation growth factor receptor alpha (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue after 7 d. Results: The levels of TGF-β1, IL-1β in all poisoning groups went up first and then went down. The levels of TGF-β1, IL-1β in associated group at 1, 3, 7 d were lower than that of PQ poisoning group, Shenfu Injection group and Nintedanib group at the same point (P<0.05). Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group, Nintedanib group and associated group were milder than that of PQ poisoning group, and the midest in associated group. Compared with control group, the W/D of lung tissue was higher, the level of MDA in lung tissue was higher, while the level of SOD was lower, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were higher in PQ poisoning group (P<0.05). Compared with PQ poisoning group, Shenfu Injection group and Nintedanib group, the W/D of lung tissue was lower, the level of MDA in lung tissue was lower, while the level of SOD was higher, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were lower in associated group (P<0.05) . Conclusion: Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ, which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1, PDGFRα, VEGFR2 in lung tissue of rats.

Serum metabolomics characteristics and fatty-acid-related mechanism of cirrhosis with histological response in chronic hepatitis B.

Background and aims: The serum metabolites changes in patients with hepatitis B virus (HBV)-related cirrhosis as progression. Peroxisome proliferator-activated receptor gamma (PPARγ) is closely related to lipid metabolism in cirrhotic liver. However, the relationship between fatty acids and the expression of hepatic PPARγ during cirrhosis regression remains unknown. In this study, we explored the serum metabolic characteristics and expression of PPARγ in patients with histological response to treatment with entecavir. Methods: Sixty patients with HBV-related cirrhosis were selected as the training cohort with thirty patients each in the regression (R) group and non-regression (NR) group based on their pathological changes after 48-week treatment with entecavir. Another 72 patients with HBV-related cirrhosis and treated with entecavir were collected as the validation cohort. All of the serum samples were tested using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Data were processed through principal component analysis and orthogonal partial least square discriminant analysis. Hepatic PPARγ expression was observed using immunohistochemistry. The relationship between serum fatty acids and PPARγ was calculated using Pearson's or Spearman's correlation analysis. Results: A total of 189 metabolites were identified and 13 differential metabolites were screened. Compared to the non-regression group, the serum level of fatty acids was higher in the R group. At baseline, the expression of PPARγ in hepatic stellate cells was positively correlated with adrenic acid (r 2 = 0.451, p = 0.046). The expression of PPARγ in both groups increased after treatment, and the expression of PPARγ in the R group was restored in HSCs much more than that in the NR group (p = 0.042). The adrenic acid and arachidonic acid (AA) in the R group also upgraded more than the NR group after treatment (p = 0.037 and 0.014). Conclusion: Baseline serum differential metabolites, especially fatty acids, were identified in patients with HBV-related cirrhosis patients who achieved cirrhosis regression. Upregulation of adrenic acid and arachidonic acid in serum and re-expression of PPARγ in HSCs may play a crucial role in liver fibrosis improvement.

Comparison on different traditional Chinese medicine therapies for chronic hepatitis B liver fibrosis.

Background and Aims: Although different kinds of traditional Chinese medicines could reportedly improve the efficacy of antiviral therapy on liver fibrosis caused by HBV, the problem of clinicians on how to choose the appropriate treatment strategies for the patients fails to be solved. This study aims at comparing and ranking different traditional Chinese medicine (TCM) therapies in the treatment of liver fibrosis due to chronic hepatitis B (CHB). Methods: Eight electronic databases were searched from their establishment to 17 Aug 2021. All included data and pooled odds ratio were used for network meta-analysis (NMA) and statistical analysis. The consistency was evaluated by the node-splitting analysis. The stability of results and source of heterogeneity were tested by sensitivity analysis. Different treatment strategies (regimens) in this network meta-analysis were ranked with the aid of surface under the cumulative ranking curve (SUCRA) probability value. Results: A total of 29 articles with 3,106 sufferers were recruited in this NMA. Results of SUCRA value rankings indicated that Fuzheng Huayu therapy or combined with entecavir had preferable effects in improving the clinical efficacy, recovering the level of hyaluronic acid, IV-C, ALT, ALB, and TBil, relieving the TCM symptoms including hypochondriac pain and poor appetite, regaining the width of portal vein and thickness of spleen, and lessening side effects. Apart from these, Ziyin Shugan therapy or combined with ETV could also be suitable to regain the level of laminin, PC-III, and AST, relieve fatigue and HBV-DNA conversion. Conclusion: This NMA confirmed the efficacy and safety of different treatment therapies for improving CHB liver fibrosis, including the serum biomarkers of live fibrosis and serum parameters for liver function, TCM symptoms, imaging indexes, HBV-DNA conversion rate, which offered the TCM practitioners crucial reference value on clinical medication.

Targeted delivery of maytansine to liver cancer cells via galactose-modified supramolecular two-dimensional glycomaterial.

A two-dimensional (2D) glycomaterial for targeted delivery of maytansine to liver cancer cells was developed. Host-guest interaction between a galactosyl dye and human serum albumin (HSA) produces supramolecular galactoside-HSA conjugates, which are then used to coat 2D MoS2. The 2D glycomaterial was shown to be capable of the targeted delivery of maytansine to a liver cancer cell line that highly expresses a galactose receptor, resulting in greater cytotoxicity than maytansine alone.