Predicting anion diffusion in bentonite using hybrid machine learning model and correlation of physical quantities.

Radionuclide diffusion will be influenced by numerous factors. Establishing a model that can elucidate the internal correlation between mesoscopic diffusion and the microscopic structure of bentonite can enhance the comprehension of radionuclide diffusion mechanisms. In this study, a light gradient boosting machine (LightGBM) was employed to predict the effective diffusion coefficients of HCrO4-, I-, and CoEDTA2- in bentonite. The model's hyperparameters were optimized using the particle swarm optimization (PSO) algorithm. Several correlated physical quantities, such as mesoscopic parameters (total porosity, rock capacity factor, and ion molar conductivity) and microscopic parameters (ionic radius and montmorillonite stacking number) were incorporated to develop a machine learning model that incorporated micro- and meso-scale features. The predictive performance of PSO-LightGBM was verified using diffusion experiments, which investigated the diffusion of HCrO4-, I-, and CoEDTA2- at compacted dry densities of 1200-1800 kg/m3 using a through-diffusion method. Spearman correlation and Shapley additive explanation analyses revealed that the compacted dry density, ionic diffusion coefficient in water, ionic radius, and total porosity were the top-four influencing factors among the 16 input features. Partial dependence plot analysis elucidated the relationship between the effective diffusion coefficient and each input feature. The analysis results were consistent with the experimental findings, demonstrating the reliability of machine learning. Due to the incorporation of multi-scale features, the PSO-LightGBM model demonstrated enhanced predictive accuracy, linking the microstructure of bentonite to radionuclide diffusion, and providing a comprehensive interpretation of the diffusion mechanism.

NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody.

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for successful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mammalian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinucleation and midbody disorganization. Using iTRAQ-based quantitative proteomic analysis, we find that RCC2 levels are decreased in NudCL2 knockout (KO) cells. Moreover, Hsp90 forms a complex with NudCL2 to stabilize RCC2, which is essential for cytokinesis. RCC2 depletion mirrors phenotypes observed in NudCL2-downregulated cells. Importantly, ectopic expression of RCC2 rescues the cytokinesis defects induced by NudCL2 deletion, but not vice versa. Together, our data reveal the significance of the NudCL2/Hsp90/RCC2 pathway in cytokinesis at the midbody.

Effects and mechanisms of acupuncture on women related health.

Globally, public health interventions have resulted in a 30-year increase in women's life expectancy. However, women's health has not increased when socioeconomic status is ignored. Women's health has become a major public health concern, for those women from developing countries are still struggling with infectious and labor-related diseases, and their counterparts in developed countries are suffering from physical and psychological disorders. In recent years, complementary and alternative medicine has attracted wide attentions with regards to maintaining women's health. Acupuncture, a crucial component of traditional Chinese medicine, has been used to treat many obstetric and gynecological diseases for thousands of years due to its analgesic and anti-inflammatory effects and its effects on stimulating the sympathetic/parasympathetic nervous system. To fully understand the mechanism through which acupuncture exerts its effects in these diseases would significantly extend the list of available interventions and would allow for more reasonable advice to be given to general practitioners. Therefore, by searching PubMed and CNKI regarding the use of acupuncture in treating obstetric and gynecological diseases, we aimed to summarize the proven evidence of using acupuncture in maintaining women's health by considering both its effectiveness and the underlying mechanisms behind its effects.

Combined Amphiphilic Silybin Meglumine Nanosuspension Effective Against Hepatic Fibrosis in Mice Model.

Introduction: Silybin (SLB) as an effective hepatoprotective phytomedicine has been limited by its hydrophobicity, poor bioavailability and accumulation at lesion sites. Additionally, present drug loading methods are impeded by their low drug loading capacity, potential hazard of materials and poor therapeutic effects. Consequently, there is a pressing need to devise an innovative approach for preparing nanosuspensions loaded with both SLB and Silybin Meglumine salt (SLB-M), as well as to investigate the therapeutic effects of SLB nanosuspensions against hepatic fibrosis. Methods: The SLB nanosuspension (NS-SLB) was prepared and further modified with a hyaluronic acid-cholesterol conjugate (NS-SLB-HC) to improve the CD44 targeting proficiency of NS-SLB. To validate the accumulation of CD44 and ensure minimal cytotoxicity, cellular uptake and cytotoxicity assessments were carried out for the nanosuspensions. Western blotting was employed to evaluate the anti-hepatic fibrosis efficacy in LX-2 cells by inhibiting the secretion of collagen I. Hepatic fibrosis mouse models were used to further confirm the effectiveness of NS-SLB and NS-SLB-HC against hepatic fibrosis in vivo. Results: Uniform nanosuspensions were prepared through self-assembly, achieving high drug loading rates of 89.44% and 60.67%, respectively. Both SLB nanosuspensions showed minimal cytotoxicity in cellular environments and mitigated hepatic fibrosis in vitro. NS-SLB-HC was demonstrated to target activated hepatic stellate cells by receptor-ligand interaction between HA and CD44. They can reverse hepatic fibrosis in vivo by downregulating TGF-ß and inhibiting the secretion of α-SMA and collagen I. Conclusion: Designed as a medical excipient analogue, SLB-M was aimed to establish an innovative nanosuspension preparation method, characterized by high drug loading capacity and a notable impact against hepatic fibrosis.

Corrigendum: NudC L279P mutation destabilizes filamin a by inhibiting the Hsp90 chaperoning pathway and suppresses cell migration.

[This corrects the article DOI: 10.3389/fcell.2021.671233.].

Predictors for short-term successful weaning from continuous renal replacement therapy: a systematic review and meta-analysis.

The systemic review and meta-analysis aimed to identify the predictors for short-term successful weaning from CRRT in severe AKI patients. PubMed, Embase, the Cochrane Library, and grey literature were searched for relevant studies investigating variables for short-term successful weaning from CRRT to August 2022. Our criteria included patients with AKI who required CRRT but excluded patients with kidney failure. The pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed-effect (I2≤50% and P-value of the Q statistic > 0.1) or random-effect models (I2>50% or p-value of the Q statistic ≤ 0.1) as appropriate. Our search yielded 11 studies and described 11 variables. The pooled analysis showed that chronic kidney disease (OR = 0.638, 95% CI: 0.491-0.829), CRRT duration (OR = 0.913, 95% CI: 0.882-0.946), and urine output at the cessation of CRRT (per 100 mL/day increase) (OR = 1.084, 95% CI: 1.061-1.108) were predictive factors for short-term successful weaning from CRRT. Male (OR = 0.827, 95% CI: 0.627-1.092), diabetes mellitus (OR = 0.970, 95% CI: 0.761-1.237), and sepsis (OR = 0.911, 95% CI: 0.717-1.158) were unrelated to the short-term weaning from CRRT. The relationship between hypertension, use of vasopressors or inotropes at the starting of CRRT, use of vasopressors or inotropes at the cessation of CRRT, use of diuretics at the cessation of CRRT, serum creatinine at the cessation of CRRT, and short-term weaning from CRRT remains unclear. Additional prospective studies are needed to evaluate this relationship further.

Palmitic acid-modified human serum albumin paclitaxel nanoparticles targeting tumor and macrophages against breast cancer.

Breast cancer is the most common malignant tumor in women, and the liver is the main target organ for breast cancer metastasis. Once metastasis occurs, the prognosis is very poor. The uptake of PSA NPs made by our synthesized Palmitic acid-modified human serum albumin (PSA) in macrophages is about 15 times higher than that of HSA NPs. As a first-line chemotherapeutic drug, paclitaxel not only does not kill macrophages, but it can also polarize macrophages into classically activated macrophages (M1). We combined these two characteristics into PTX-PSA NPs, which achieved dual targeting of macrophages and tumor cells, improved the tumor microenvironment, and achieved a more effective anti-breast cancer drug effect than PTX-HSA NPs. On this basis, we also used the pathological characteristics of low vascular perfusion of breast cancer liver metastasis, and used the characteristics of macrophages that can release paclitaxel after internalizing paclitaxel, and use macrophages as the delivery system of breast cancer liver metastasis. Therefore,PTX-PSA NPs is better than PTX-HSA NPs to achieve anti-breast cancer liver metastasis.

The efficacy and mechanism of acupuncture in the treatment of male infertility: A literature review.

Fertility, a social, cultural, and medical issue, has aroused public attention because of its potential to predict future health. In recent years, the incidence of male infertility has increased significantly, and various risk factors, such as congenital factors, acquired factors, and idiopathic factors, have led to this situation. Male infertility causes substantial psychological and social distress in patients. With the implementation of the two-child policy, male infertility has brought enormous psychological and social pressure and huge economic burden to patients and the healthcare system. This has attracted the attention of not only men of childbearing age but also many male experts. The conventional therapeutic approaches for treating male infertility, including drugs, varicocele surgery, intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection, can restore fertility to a certain extent, but their efficacy is far from satisfactory, not to mention some adverse events. Therefore, acupuncture has been chosen by many men to treat their infertility and produced significant effects. In the present paper, the efficacy and mechanism of acupuncture in the treatment of male infertility were analyzed from different perspectives such as regulating hormone secretion, reducing inflammation, and improving semen parameters. The existing literature shows that acupuncture can effectively treat male infertility.

[Value of Blood Urea Nitrogen-to-Creatinine Ratio for Differentiating the Site of Gastrointestinal Bleeding and Assessing the Prognosis of Patients with Acute Nonvariceal Upper Gastrointestinal Bleeding].

Objective: To explore the diagnostic performance of blood urea nitrogen-to-creatinine (BUN/Cr) ratio in differentiating the site of gastrointestinal bleeding, and to assess the predictive value of early elevated BUN/Cr ratio for clinical outcomes in patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB). Methods: The adult patients diagnosed with gastrointestinal bleeding who were hospitalized in the Department of Gastroenterology, Zhongshan Hospital, Xiamen University between May 2020 and May 2021 were retrospectively enrolled. According to the site of gastrointestinal bleeding, the patients were divided into the upper gastrointestinal tract group, the proximal small intestinal bleeding group, and the distal small intestinal and colonic bleeding group. According to the early dynamic changes of BUN/Cr ratio within 6-48 hours after admission, patients with ANVUGIB were divided into early dynamic elevated BUN/Cr ratio group and non-early dynamic elevated BUN/Cr ratio group. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of BUN/Cr ratio in differentiating the site of gastrointestinal bleeding and examine the predictive efficacy of early dynamic elevated BUN/Cr ratio after admission, Rockall scoring system, and the combined indicator of the two for estimating the primary clinical outcomes in ANVUGIB patients. Results: A total of 266 patients were enrolled. Among them, 204 cases were in the upper gastrointestinal bleeding group, 15 cases were in the proximal small intestinal bleeding group, and 47 cases were in the distal small intestinal and colonic bleeding group. In the ANVUGIB patients, 16 were in the group with early dynamic elevated BUN/Cr ratio after admission, and 146 were in the group with non-early dynamic elevated BUN/Cr ratio after admission. The area under the ROC curve of the BUN/Cr ratio was 0.831 (95% CI: 0.780-0.874), the optimal cut-off value being 34.59 mg/g for differentiation between upper and lower gastrointestinal bleeding. The area under the ROC curve of the BUN/Cr ratio was 0.901 (95% CI: 0.798-0.963) and the optimal cut-off value was 19.27 mg/g for differentiation between proximal small intestinal bleeding and the distal small intestinal and colonic bleeding. The area under the ROC curve of the early dynamic elevated BUN/Cr ratio after admission was 0.806 (95% CI: 0.737-0.864) for predicting the primary clinical outcome in patients with ANVUGIB. The area under the ROC curve of the combined indicator included the early dynamic elevated BUN/Cr ratio after admission and the Rockall scoring system was 0.909 (95% CI: 0.854-0.949) for predicting the primary clinical outcome in patients with ANVUGIB. Conclusion: The BUN/Cr ratio shows rather reliable diagnostic performance for identifying the site of gastrointestinal bleeding, and the early dynamic elevated BUN/Cr ratio after admission is a reliable indicator for predicting clinical outcomes in patients with ANVUGIB.

Metabolome analysis of genus Forsythia related constituents in Forsythia suspensa leaves and fruits using UPLC-ESI-QQQ-MS/MS technique.

Forsythia suspensa is a traditional Chinese herb. Its numerous metabolites have important roles, as they possessed a wide range of biological activities. This study explored the accumulations of F. suspensa metabolites by performing widely targeted metabolomic analysis. The metabolites were studied at four stages of fruit development. Metabolites in the fruits and leaves of F. suspensa during fruit development included phenolic acids, flavonoids, lipids, lignans and coumarins, amino acids and their derivatives, terpenes, organic acids, nucleotides and their derivatives, alkaloids, quinones, steroids, and tannins. Fourteen Forsythia related metabolites were detected. Their contents varied among the developmental stages. Statistically significant correlations were found between the levels of forsythoside B and 11-methyl-forsythide, and forsythialan B and phillygenin, in both leaves and fruits. According to the correlation analysis between metabolites, Forsythia related metabolites were divided into two classes and five subclasses. In total, 33 compounds presented significant correlations in both fruits and leaves, which indicated the potential relationship in the synthesis of Forsythia related metabolites. Forsythialan B and phillygenin were both negatively correlated with L-valine, while Z-6,7-epoxyligustilid was positively correlated with both compounds. The quality control compounds forsythiaside A and phillyrin were positively and negatively correlated with uracil, respectively. These metabolomics results may facilitate the biosynthesis of Forsythia related metabolites.

Dual-Targeting of Tumor Cells and Tumor-Associated Macrophages by Palmitic Acid Modified Albumin Nanoparticles for Antitumor and Antimetastasis Therapy.

Tumor-associated macrophages (TAMs), the most abundant immune cells in the tumor microenvironment (TME), profoundly affect the occurrence and development of tumors. To overcome the common limitations of TAMs-targeted delivery systems, such as off-target toxicity, high cost, and transformation probability, we fabricated pirarubicin (THP)-loaded palmitic acid modified human serum albumin nanoparticles (THP-PSA NPs) for dual-targeting of tumor cells and TAMs via acidic secretory proteins rich in cysteine (SPARC) and scavenger receptor-A (SR-A), respectively. In vitro, the THP-PSA NPs exhibit stronger cytotoxicity against 4T1 and M2 macrophages compared with THP-loaded human serum albumin nanoparticles (THP-HSA NPs). In vivo, the infiltration of myeloid-derived suppressor cells (MDSCs) and the secretion of immunosuppressive cytokines significantly decrease after effective elimination of the TAMs through the THP-PSA NPs treatment; this is accompanied by an increase in the immunostimulatory cytokine expression level. Moreover, the antitumor and antimetastasis experimental results indicate that the tumor volumes in mice treated with the THP-PSA NPs are effectively controlled, resulting in an inhibition rate of 81.0% and almost no metastases in the lung tissues. Finally, in terms of biological safety, the THP-PSA NPs perform similar to THP-HSA NPs, causing no damage to the liver or kidney.

Evidence for the Use of Complementary and Alternative Medicine for Pelvic Inflammatory Disease: A Literature Review.

Pelvic inflammatory disease (PID), a common infectious disease of the female reproductive tract, is mainly characterized by abdominal/pelvic pain and tenderness of the uterus, cervix, or adnexa on physical exam. In recent years, its incidence has gradually increased yearly due to numerous factors, including sexually transmitted diseases and intrauterine operations. Based on self-report of PID in the National Health and Nutrition Examination Survey (NHANES) 2013-2014 survey, PID impacts approximately 2.5 million women in the US during their reproductive age. Although empiric treatments such as antibiotics or surgery could alleviate the related symptoms of PID, its unsatisfactory obstetric outcome and high relapse bring heavy physical and psychological burden to women. Complementary and alternative medicine (CAM), a complementary therapy other than Western medicine with a complete theoretical and practical system, has been attached to importance in the world due to its remarkable efficacy. More people are accepting and trying to use CAM to treat gynecological diseases, including infertility, polycystic ovary syndrome, and PID, but its efficacy and mechanism are still controversial. This article reviews the previous literature systematically focusing on the effectiveness, safety, and mechanism of CAM in the treatment of PID to provide an evidence-based basis for the clinical application of CAM in patients with PID.

Targeted delivery of celastrol to glomerular endothelium and podocytes for chronic kidney disease treatment.

The etiology of chronic kidney disease (CKD) is complex and diverse, which could be briefly categorized to glomerular- or tubular-originated. However, the final outcomes of CKD are mainly glomerular sclerosis, endothelial dysfunction and injury, and chronic inflammation. Thus, targeted delivery of drugs to the glomeruli in order to ameliorate glomerular endothelial damage may help alleviate CKD and help enrich our knowledge. The herb tripterygium wilfordii shows therapeutic effect on kidney disease, and celastrol (CLT) is one of its active ingredients but with strong toxicity. Therefore, based on the unique structure and pathological characteristics of the glomerulus, we designed a targeted delivery system named peptides coupled CLT-phospholipid lipid nanoparticles (PC-PLNs) to efficiently deliver CLT to damaged endothelial cells and podocytes in the glomerulus for CKD treatment and research. PC-PLNs could effectively inhibit inflammation, reduce endothelial damage, alleviate CKD severity, and reduce the toxicity of CLT. We also studied the mechanism of CLT in the treatment of nephropathy and found that CLT can increase the level of NO by increasing eNOS while inhibiting the expression of VCAM-1, thus provides an anti-inflammatory effect. Therefore, our study not only offered an efficient CKD drug formulation for further development, but also provided new medical knowledge about CKD. Electronic Supplementary Material: Supplementary material (attached with all the supporting tables and figures mentioned in this work) is available in the online version of this article at 10.1007/s12274-021-3894-x.

Chondroitin sulfate-mediated albumin corona nanoparticles for the treatment of breast cancer.

Chondroitin sulfate-mediated albumin corona nanoparticles were readily prepared without any chemical reaction, and their active tumor targeting and therapeutic effects were examined. Negatively charged chondroitin sulfate (CS) and positively charged doxorubicin (DOX) self-assembled into nanoparticles (CS-DOX-NPs) via electrostatic interactions. Bovine serum albumin (BSA) was then adsorbed on the surface of CS-DOX-NPs to form albumin corona nanoparticles (BC-DOX-NPs) protected from endogenous proteins. Due to the dual effect of BSA and CS, BC-DOX-NPs interacted with the gp60, SPARC and CD44 receptors on tumor cells, facilitating their rapid and efficient transcytosis and improving their accumulation and uptake within tumor tissues. The simultaneous presence of BSA and CS also allowed BC-DOX-NPs to target CD44 efficiently, leading to greater cellular uptake and cytotoxicity against 4T1 cells than CS-DOX-NPs or free DOX. Intravenous injection of BC-DOX-NPs into orthotopic 4T1 tumor-bearing mice led to greater drug accumulation at the tumor site than with CS-DOX-NPs or free DOX, resulting in significant inhibition of tumor growth and lower exposure of major organs to the drug.

NudCL2 is an autophagy receptor that mediates selective autophagic degradation of CP110 at mother centrioles to promote ciliogenesis.

Primary cilia extending from mother centrioles are essential for vertebrate development and homeostasis maintenance. Centriolar coiled-coil protein 110 (CP110) has been reported to suppress ciliogenesis initiation by capping the distal ends of mother centrioles. However, the mechanism underlying the specific degradation of mother centriole-capping CP110 to promote cilia initiation remains unknown. Here, we find that autophagy is crucial for CP110 degradation at mother centrioles after serum starvation in MEF cells. We further identify NudC-like protein 2 (NudCL2) as a novel selective autophagy receptor at mother centrioles, which contains an LC3-interacting region (LIR) motif mediating the association of CP110 and the autophagosome marker LC3. Knockout of NudCL2 induces defects in the removal of CP110 from mother centrioles and ciliogenesis, which are rescued by wild-type NudCL2 but not its LIR motif mutant. Knockdown of CP110 significantly attenuates ciliogenesis defects in NudCL2-deficient cells. In addition, NudCL2 morphants exhibit ciliation-related phenotypes in zebrafish, which are reversed by wild-type NudCL2, but not its LIR motif mutant. Importantly, CP110 depletion significantly reverses these ciliary phenotypes in NudCL2 morphants. Taken together, our data suggest that NudCL2 functions as an autophagy receptor mediating the selective degradation of mother centriole-capping CP110 to promote ciliogenesis, which is indispensable for embryo development in vertebrates.

Risk Factors for Vitamin D Deficiency in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: To identify risk factors for hypovitaminosis D in inflammatory bowel disease and conduct a comprehensive systematic review with meta-analysis to quantify the impact on vitamin D deficiency. METHODS: We conducted a literature search of studies through PubMed, Embase, Cochrane Library, and Web of Science. In addition, relevant articles were searched manually. Studies were included if the odds ratios (OR) and 95% CI of each risk factor were reported or could be calculated. We will use the fixed-effects or random-effects model to estimate the pooled effect. RESULTS: Out of 1018 articles, 25 eligible studies were identified, including 5826 participants. The risk factors associated with hypovitaminosis D were non-Caucasian (OR: 3.79, 95% CI: 2.68-5.34), Crohn's disease (OR: 1.38, 95% CI: 1.21-1.56), disease activity (OR: 1.85, 95% CI: 1.61-2.13), inflammatory bowel disease-related surgery (OR: 1.61, 95% CI: 1.38-1.89), exposure to steroid (OR: 1.61, 95% CI: 1.28-2.03), and biologics (OR: 1.78, 95% CI: 1.48-2.14). In 30 ng/mL and adjusted OR subgroup, male (OR: 1.84, 95% CI: 1.47-2.31) and winter season (OR: 2.49, 95% CI: 1.69-3.67) also were risk factors, respectively. 5-aminosalicylic acid (OR: 1.10, 95% CI: 0.74-1.63) and smoking (OR: 1.19, 95% CI: 0.98-1.45) were unrelated to vitamin D deficiency. CONCLUSIONS: For vitamin D deficiency in inflammatory bowel disease, non-Caucasian, Crohn's disease, disease activity, surgery, exposure to steroid and biologics, males are risk factors, while 5-aminosalicylic acid and smoking are not. The relationship between body mass index, winter season, exposure to immunomodulators, and vitamin D deficiency remains unclear.

NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration.

Filamin A, the first discovered non-muscle actin filament cross-linking protein, plays a crucial role in regulating cell migration that participates in diverse cellular and developmental processes. However, the regulatory mechanism of filamin A stability remains unclear. Here, we find that nuclear distribution gene C (NudC), a cochaperone of heat shock protein 90 (Hsp90), is required to stabilize filamin A in mammalian cells. Immunoprecipitation-mass spectrometry and western blotting analyses reveal that NudC interacts with filamin A. Overexpression of human NudC-L279P (an evolutionarily conserved mutation in NudC that impairs its chaperone activity) not only decreases the protein level of filamin A but also results in actin disorganization and the suppression of cell migration. Ectopic expression of filamin A is able to reverse these defects induced by the overexpression of NudC-L279P. Furthermore, Hsp90 forms a complex with filamin A. The inhibition of Hsp90 ATPase activity by either geldanamycin or radicicol decreases the protein stability of filamin A. In addition, ectopic expression of Hsp90 efficiently restores NudC-L279P overexpression-induced protein stability and functional defects of filamin A. Taken together, these data suggest NudC L279P mutation destabilizes filamin A by inhibiting the Hsp90 chaperoning pathway and suppresses cell migration.

Collagenase-loaded pH-sensitive nanocarriers efficiently remodeled tumor stroma matrixes and improved the enrichment of nanomedicines.

The dense extracellular matrix (ECM) in tumor tissue severely hinders the penetration and enrichment of antitumor nanomedicines, which could significantly affect their efficiency. In this study, we used pH-sensitive nanocarriers loaded with collagenase (Col) to remold the tumor microenvironment (TME). Furthermore, we combined the collagenase delivery system with a nanomedicine to improve its penetration and enrichment in the tumor, thereby improving efficacy. We synthesized acetalated dextran (Ace-DEX) with an ideal pH-sensitivity as the carrier material of collagenase. Under mild preparation conditions, collagenase was loaded into Ace-DEX nanoparticles (NPs) with a high loading capacity (>4%) and remained highly active (>90%). Col-carrying NPs (Col-NPs) significantly reduced the tumor collagen content by 15.1%. Pretreatment with Col-NPs increased the accumulation of doxorubicin (DOX)-loaded liposome (DOX-Lipo) in the tumor by 2.8-fold. There were no safety concerns as the Col-NP showed no significant toxicity and reduced Col-induced damage to healthy tissues. Additionally, the number of circulating tumor cells remained unchanged after Col-NP treatment, suggesting no increased risk of tumor metastasis. Because the Col-NP acts essentially independent of the subsequent treatment, it has considerable potential for enhancing many existing delivery systems and drugs for cancer treatment. It may also be used for treating other collagen-related diseases.

The Efficacy of Complementary and Alternative Medicine in the Treatment of Female Infertility.

Female infertility is a state of fertility disorder caused by multiple reasons. The incidence of infertility for females has significantly increased due to various factors such as social pressure, late marriage, and late childbirth, and its harm includes heavy economic burden, psychological shadow, and even marriage failure. Conventional solutions, such as hormone therapy, in vitro fertilization (IVF), and embryo transfer, have the limitations of unsatisfied obstetric outcomes and serious adverse events. Currently, complementary and alternative medicine (CAM), as a new treatment for infertility, is gradually challenging the dominant position of traditional therapies in the treatment of infertility. CAM claims that it can adjust and harmonize the state of the female body from a holistic approach to achieve a better therapeutic effect and has been increasingly used by infertile women. Meanwhile, some controversial issues also appeared; that is, some randomized controlled trials (RCTs) confirmed that CAM had no obvious effect on infertility, and the mechanism of its effect could not reach a consensus. To clarify CAM effectiveness, safety, and mechanism, this paper systematically reviewed the literature about its treatment of female infertility collected from PubMed and CNKI databases and mainly introduced acupuncture, moxibustion, and oral Chinese herbal medicine. In addition, we also briefly summarized psychological intervention, biosimilar electrical stimulation, homeopathy, hyperbaric oxygen therapy, etc.

The Complementary and Alternative Medicine for Polycystic Ovary Syndrome: A Review of Clinical Application and Mechanism.

As a reproductive endocrine disease, polycystic ovary syndrome (PCOS) has influenced billions of women during childbearing age worldwide. Owing to its complex etiology and ambiguous pathogenesis, there is still not a specific method to cure it. Clinical treatments, such as hormone therapy and surgical treatment, have side effects. Therefore, it is essential and urgent to seek alternative treatment to solve these problems. The satisfactory efficacy of complementary and alternative medicine (CAM), such as traditional Chinese medicine (TCM), immunotherapy, medicinal foods, vitamin therapy, diet therapy, psychotherapy, spa, and oxygen therapy, in treating PCOS, has aroused an increasing number of medical workers' concern and gradually become the mainstream. This paper reviews the application of CAM in the treatment of PCOS, especially from the perspective of TCM. Meanwhile, the limitations of the literature about CAM in the treatment of PCOS are mentioned and analyzed as well.