Clinical Results of Asymmetric Blepharoplasty Plastic Repair.

OBJECTIVE: To investigate plastic surgery repair's effects and adverse reactions in the clinical therapy of asymmetric double eyelids. METHODS: All 126 sufferers who came to the hospital for asymmetric double eyelid plastic repair from January 2022 to October 2022 were selected as the research objects, and they were divided into a control group and an observation group using the random number method, with 63 cases in each group, in which sufferers in the control group underwent full incision blepharoplasty and sufferers in the observation group underwent small incision liposuction with submerged sutures. The general data, treatment results, treatment satisfaction, related surgical indicators, and frequency of adverse reactions of the 2 groups of sufferers with asymmetric double eyelid plastic repair were compared. RESULTS: It had no statistically obvious distinction between the control group and the observation group of sufferers in terms of general data such as sex, age, weight, and height (P>0.05); the total therapy efficiency of the sufferers in the observation group (95.24%) was greater than the control group (74.60%), with P value <0.05; the total treatment satisfaction of the patients in the observation group (96.83%) was significantly higher than that in the control group (76.19%), with P value <0.05; compared with the control group, patients in the observation group had shorter operative time and healing time and less intraoperative bleeding, with P value <0.05; the total frequency of adverse reactions of sufferers in the observation group (4.76%) was less than the control group (17.46%), with P value <0.05. CONCLUSION: Small incision liposuction with submerged sutures for plastic repair has significant efficacy, relatively high patient satisfaction, and low incidence of adverse reactions, in line with patient esthetic review, which has a broad clinical application prospect.

Coronavirus disease-2019 and orthopedics: A bibliometric analysis of the literature.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has had a dramatic impact on global health, with orthopedics among the most affected specialties. An increasing number of COVID-19-related orthopedic studies have been published. The purpose of this study was to analyze the orthopedic literature published during the COVID-19 pandemic to guide future research. METHODS: The Scopus database was searched for relevant literature published between 2020 and 2022. The keywords used in the retrieval process were ("COVID-19" OR "Coronavirus" OR "2019-nCoV" OR "SARS-CoV-2" OR "Betacoronavirus" OR "novel coronavirus 2019" OR "novel coronavirus" OR "coronavirus-19" OR "COVID 19" OR "nCOV" OR "COVID-2019" OR "COVID 2019") and ("orthopedic" OR "orthopedics" OR "orthopedic" OR "orthopedical" OR "orthopedical" OR "orthopedics"). Spreadsheet software (Excel, Microsoft Corp., Redmond, WA) was used to analyze the top 10 cited authors, countries, journals, and articles. The top 5 publication types were also analyzed. VOSviewer (Center for Science and Technology Studies, Leiden, Netherlands) was used to network and visualize the literature. RESULTS: A total of 1619 publications relevant to COVID-19 and orthopedics were reviewed. Among these publications, the most active country, author, and publication type included the United States, Vaishya R, and original articles, respectively. The most frequently used keywords were human, coronavirus disease-2019, pandemic, and orthopedics. The Journal of Bone and Joint Surgery American Volume was the most cited journal, whereas the greatest number of articles was published in the Journal of Clinical Orthopedics and Trauma. CONCLUSIONS: This study provides a perspective on the development of orthopedic publications during the COVID-19 pandemic and evidence for researchers worldwide to strengthen global cooperation in fighting the epidemic.

[Research progress of femoral bone tunnel positioning in anterior cruciate ligament reconstruction].

Objective: To review the concept and methods of femoral bone tunnel positioning in anterior cruciate ligament (ACL) reconstruction, in order to provide a reference for clinical treatment. Methods: The relevant literature on the concept and methods of femoral bone tunnel positioning in ACL reconstruction in domestic and international research was extensively reviewed. Results: The position of the femoral bone tunnel is a key factor in determining the prognosis of ACL reconstruction. The concept of femoral bone tunnel positioning in ACL reconstruction has experienced isometric reconstruction, anatomical reconstruction, Ribbon-like theory, I.D.E.A.L. theory, and nearly isometric reconstruction theory. The femoral bone tunnel positioning technique is also changing with the in-depth study of the anatomy and biomechanics of the ACL, and each bone tunnel positioning technique has its own advantages and disadvantages. Over-The-Top technique is now mainly used for ACL revision; the clock-face positioning method is basically no longer applicable due to the large error, poor stability, and low retrievability; the bone landmarks positioning method (the lateral condyle of the femur's Resident's ridge and bifurcation ridge, and the the apex of the deep cartilage), which is now mostly used clinically due to the more constant anatomical landmarks. The quadrant method under X-ray fluoroscopy is more cumbersome to implement intraoperatively, so it is mainly used for academic research; computer navigation-assisted positioning has gradually become popular in recent years, which is highly accurate, avoids the influence of human factors on the positioning of the bone tunnel, and has a very good prospect of application; three-dimensional printing-assisted positioning technology, which is accurate in positioning, with a high degree of reproducibility and a short learning curve. Conclusion: The concept of femoral bone tunnel positioning for ACL reconstruction has undergone several evolutions, reflecting the deepening of the understanding of ACL and the improvement of the clinical results of reconstruction. The precision, personalization, and intelligence of positioning techniques are the focus of current and future development.

Engineered protein cages with enhanced extracellular drug release for elevated antitumor efficacy.

Human heavy chain ferritin (HFn) protein cage has been explored as a nanocarrier for targeted anticancer drug delivery. Here, we introduced a matrix metalloproteinases (MMPs)-cleavable sequence into the DE loop of HFn, creating an MMP-responsive variant, MR-HFn, for localized and extracellular drug release. The crystal structure of MR-HFn revealed that the addition of the MMPs recognition sequence did not affect the self-assembly of HFn but presented a surface-exposed loop susceptible to MMPs cleavage. Biochemical analysis indicated that this engineered protein cage is responsive to MMPs, enabling the targeted release of encapsulated drugs. To evaluate the therapeutic potential of this engineered protein cage, monosubstituted ß-carboxy phthalocyanine zinc (CPZ), a type of photosensitizer, was loaded inside this protein cage. The prepared CPZ@MR-HFn showed higher uptake and stronger phototoxicity in MMPs overexpressed tumor cells, as well as enhanced penetration into multicellular tumor spheroids compared with its counterpart CPZ@HFn in vitro. In vivo, CPZ@MR-HFn displayed a higher tumor inhibitory rate than CPZ@HFn under illumination. These results indicated that MR-HFn is a promising nanocarrier for anticancer drug delivery and the MMP-responsive strategy here can also be adapted for other stimuli.

High flexion femoral side remnant preservation positioning technique: a new method for positioning the femoral tunnel in anterior cruciate ligament reconstruction.

PURPOSE: The aim of this study is to find a new method for femoral side preservation positioning in anterior cruciate ligament (ACL) reconstruction and test the accuracy and precision of this method. METHOD: Fifty patients with isolated ACL rupture (42 males and 8 females) who underwent single-bundle ACL reconstruction in our hospital between July 2022 and July 2023 were included. The lowest point of the cartilage margin of the lateral wall of the intercontinental fossa and the tibial plateau plumb line at 120° of knee flexion were used as the anatomical landmarks for positioning of the femoral tunnel for ACL reconstruction surgery. Femoral side remnant preservation was performed in all cases. Three-dimensional CT was performed 3 days postoperatively to collect the data, which were analyzed using Mimics 21.0 software. We measured the posterior cortical distance of the femoral condyle at 90° of knee flexion and the vertical distance from the center of the bone tunnel to the cortical extension line behind the femur. All femoral tunnel positions were marked on a 4 × 4 grid and visualized using the quadrant method. RESULTS: Using the new positioning method in 50 knees, the average distance of x was 25.26 ± 2.76% of t and the average distance of y was 23.69 ± 6.19% of h. This is close to the results of previous studies, where x was 24.2 ± 4.0% of t and the average distance of y was 21.6 ± 5.2% of h. Most femoral tunnel positions were located in the same area. The D values were distributed as follows: 60% in the range of 0 to 2 mm, 24% in the range of 2 to 4 mm, and 16% more than 4 mm. The E values were distributed as follows: 80% in the range of 0 to 4 mm and 20% more than 4 mm. CONCLUSION: In arthroscopic ACL reconstruction, the knee was flexed at 120° and the lowest point of the cartilage edge of the lateral wall of the intercondylar fossa and the tibial plateau plumb line were used as anatomical landmarks for the positioning of the femoral bone tunnel, which resulted in more accurate femoral bone tunnel positioning, better reproducibility, and better preservation of the femoral stump compared to traditional positioning methods.

An integrated approach based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, network pharmacology, and molecular docking to study the key effective compounds and mechanism of action of Platycodi Radix in the treatment of chronic obstructive pulmonary disease.

Platycodi Radix (PR) is a valuable herb that is widely used in the treatment of chronic obstructive pulmonary disease in clinics. However, the mechanism of action for the treatment of chronic obstructive pulmonary disease remains unclear due to the lack of in vivo studies. Our study established a novel integrated strategy based on ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry, network pharmacology, and molecular docking to systematically analyze the tissue distribution and active compounds of PR in vivo and the therapeutic mechanism of chronic obstructive pulmonary disease. First, tissue distribution studies have shown that the lung is the organ with the highest distribution of PR compounds. Subsequently, network pharmacology results showed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and mitogen-activated protein kinase signaling pathway were the critical mechanisms of PR against chronic obstructive pulmonary disease. Ultimately, molecular docking results showed that the key targets were stably bound to the corresponding active compounds of PR. Our study is of great significance for the screening of the key effective compounds and the study of the mechanism of action in traditional Chinese medicine and provides data to support the further development and utilization of PR.

MicroRNA-575 targets Derlin 1 to regulate proliferation, migration and invasion of human thyroid cancer cells.

Introduction: This study was undertaken to examine the expression of miR-575 in thyroid cancer tissues and to explore its therapeutic potential. Material and methods: Expression analysis was carried out by qRT-PCR. The MTT assay was used for cell viability. DAPI and annexin V/PI assays were used to detect apoptosis. Wound healing and Transwell assays were used for cell migration and invasion respectively. Western blot analysis was used to determine the expression of proteins. Results: The results showed significant downregulation of miR-575 in thyroid cancer tissues and cell lines. The role of miR-575 was deciphered by overexpression of miR-575 in MDA-T32 and MDA-T68 thyroid cancer cells. The results showed that overexpression of miR-575 caused significant inhibition of the proliferation of the MDA-T32 and MDA-T68 cells via induction of apoptotic cell death. The expression of Bax was also enhanced while that of Bax was decreased upon miR-575 overexpression in MDA-T32 and MDA-T68 cells. Additionally, miR-575 overexpression inhibited the migration and invasion of the MDA-T32 and MDA-T68 thyroid cancer cells. Bioinformatic approaches and the dual luciferase assay indicated Derlin 1 (DERL1) to be the potential target of miR-575 in thyroid cancer. DERL1 was significantly upregulated in thyroid cancer tissues and cell lines and overexpression of miR-575 caused suppression of DERL1 in MDA-T68 cells. Silencing of DERL1 inhibited the proliferation of the MDA-T68 cells while overexpression of DERL1 could abolish the effects of miR-575 overexpression on the proliferation of MDA-T68 thyroid cancer cells. Conclusions: miR-575 may be used as a therapeutic target for thyroid cancer treatment.

Comparison of Arthroscopic-Assisted Percutaneous Internal Fixation With a Modified Reducer Versus Open Reduction and Internal Fixation for Schatzker Type II and III Tibial Plateau Fractures.

Background: Tibial plateau fractures require anatomical reduction and stable fixation to achieve satisfactory results. In addition, addressing any related injuries is of paramount importance. Arthroscopic reduction and internal fixation (ARIF) has been promoted as a possible technique to treat tibial plateau fractures. Purpose: To compare the effectiveness of ARIF with this modified reducer and open reduction and internal fixation (ORIF) for Schatzker types II and III tibial plateau fractures. Study Design: Cohort study; Level of evidence, 3. Methods: We retrospectively reviewed 68 patients who were treated for Schatzker type II or III tibial plateau fractures between August 1, 2014, and October 31, 2018. Patients were categorized into the ARIF (n = 33) and ORIF groups (n = 35). The groups were compared regarding intra-articular injuries, duration of hospital stay, complications, and clinical outcomes-including the International Knee Documentation Committee (IKDC) score, the Hospital for Special Surgery (HSS) score, and range of motion (ROM). The paired t test was used to compare preoperative and postoperative data, and the chi-square test was used to compare the IKDC and HSS scores. Results: The median follow-up period was 36 months (26-40 months). Additional intra-articular lesions were found in 29 patients-21 in the ARIF group and 8 in the ORIF group (P = .02). A significant difference was observed in the duration of hospital stay-3.58 ± 1.46 days for the ARIF group and 4.57 ± 1.12 days for the ORIF group (t = -3.169; P = .002). All fractures healed within 3 months after surgery. The complication rate for all patients was 11%, with no significant difference between the ARIF and ORIF groups (t = 1.244; P = .265). At the final follow-up, there were no significant differences between the 2 groups in the IKDC score, HSS score, and ROM (P > .05 for all). Conclusion: ARIF with a modified reducer was found to be an effective, reliable, and safe procedure for the treatment of Schatzker types II and III tibial plateau fractures. Both ARIF and ORIF provided equally good results, while ARIF offered a more precise evaluation and reduced the duration of hospital stay.

Structural Dynamics-Driven Discovery of Anticancer and Antimetastatic Effects of Diltiazem and Glibenclamide Targeting Urokinase Receptor.

Diltiazem and glibenclamide are commonly used hypotensive and antidiabetic drugs. This study reports the discovery of the potential antitumor and antimetastatic effects of these two drugs using a structural dynamics-driven virtual screening targeting urokinase receptor (uPAR). Owing to uPAR's high flexibility, currently resolved crystal structures of uPAR, all in ligand-bound states, provide limited representations of its physiological conformation. To improve the accuracy of screening, we performed a long-timescale molecular dynamics simulation and obtained the representative conformations of apo-uPAR as the targets for our screening. Experimentally, we demonstrated that diltiazem and glibenclamide bound uPAR with KD values in the micromolar range. In addition, both compounds effectively suppressed tumor growth and metastasis in a uPAR-dependent manner in vitro and in vivo. This work not only provides two potent uPAR inhibitors but also reports a proof-of-concept study on the potential off-label antitumor and antimetastatic uses of diltiazem and glibenclamide.

Circular RNAs in Prostate Cancer: Is it Time to Further Explore Liquid Biopsies?

BACKGROUND: Although diagnosis and treatment of prostate cancer (PCa) have evolved rapidly in recent years, clinically significant molecular biomarkers are still needed to lower the mortality. Circular RNAs (circRNAs) are a poorly characterized component of PCa transcriptome. Recently, since the development of deep RNA sequencing and novel bioinformatic pipelines, emerging evidence suggests circRNAs to have diverse functions in the development and progression of PCa. Thus, we attempt to summarize the current situation and potential development prospects about the role of circRNAs in PCa liquid biopsies. METHODS: The role of circRNAs in PCa was summarized by searching the literature related to circRNAs in PubMed in recent years. RESULTS: Deregulation of circRNAs is associated with cell proliferation, apoptosis, cell invasion, migration, as well as metastasis in PCa. Because of the high stability and tissue specificity of circRNAs, with improved detection methodologies, circRNAs may be predictive biomarkers in liquid biopsies. CONCLUSION: From the perspective of recent research, with the development of high-throughput sequencing and novel bioinformatics tools, knowledge of circRNAs will be further expanded. Improved technologies will make personalized precision medicine less of a paper exercise. It is time to further explore circRNA in liquid biopsies.

Albumin-based drug carrier targeting urokinase receptor for cancer therapy.

Urokinase plasminogen activator receptor (uPAR) is a key participant in extracellular proteolysis, tissue remodeling and cell motility. uPAR overexpresses in most solid tumors and several hematologic malignancies, but has low levels on normal tissues, thus is advocated as a molecular target for cancer therapy. One of the obstacles for the evaluation of uPAR targeting agents in preclinical study is the species specificity, where targeting agents for human uPAR  usually not bind to murine uPAR. Here, we develop a targeting agent that binds to both murine and human uPAR. This targeting agent is genetically fused to human serum albumin, a commonly used drug carrier, and the final construct is named as uPAR targeting carrier (uPARTC). uPARTC binds specifically to uPAR-overexpressing 293T/huPAR and 293T/muPAR as demonstrated by flow cytometry. A cytotoxic compound, celastrol, is embedded into uPARTC non-covalently. The resulting macromolecular complex show effective proliferation inhibition on both murine and human uPAR overexpressing cells, and exhibit potent antitumor efficacy on hepatoma H22-bearing mice. This work demonstrates that uPARTC is a promising tumor targeting drug carrier, which address the species-specificity challenge of uPAR targeting agents and can be used to load other cytotoxic compounds.

Nafamostat Mesylate in Combination with the Mouse Amino-Terminal Fragment of Urokinase-Human Serum Albumin Improves the Treatment Outcome of Triple-Negative Breast Cancer Therapy.

Triple-negative breast cancer (TNBC) is highly aggressive and causes a higher proportion of metastatic cases. However, therapies directed to specific molecular targets have rarely achieved clinically meaningful improvements in the outcome of TNBC therapy. A urokinase-type plasminogen activator (uPA), one of the best-validated biomarkers of breast cancer, is an extracellular proteolytic serine protease involved in many pathological and physiological processes, including tumor cell invasion and metastasis. Nafamostat mesylate (NM) is a synthetic compound that inhibits various serine proteases and has been used as a therapeutic agent for the treatment of TNBC. Nevertheless, NM has poor specificity for serine proteases and is easy be hydrolyzed; moreover, the inhibitory mechanism of TNBC therapy is unclear. In this study, we combine NM with a macromolecular drug delivery vehicle, mouse amino-terminal fragment of urokinase-human serum albumin (mATF-HSA), to form a complex (mATF-HSA:NM) using the dilution-incubation-purification method. mATF specifically targets uPAR overexpressed on the surface of TNBC cells; moreover, HSA prevents NM from being hydrolyzed by numerous serine proteases. mATF-HSA:NM showed stronger inhibitory effects on the proliferation and metastasis of TNBC in vitro and in vivo without significant cytotoxicity on normal cells and tissues. In addition, we demonstrated that NM mediates metastasis of TNBC cells through inhibition of uPA using a stable uPA knockdown cell line (MDA-MB231 shuPA). Overall, we have developed a macromolecular complex targeted to treat high uPAR-expressing tumor types, and mATF-HSA can potentially be used to load other types of drugs with tumor-targeting specificity for mouse tumor models and is a promising tool to study tumor biology in mouse tumor models.

Integrated bulk and single-cell transcriptomes reveal pyroptotic signature in prognosis and therapeutic options of hepatocellular carcinoma by combining deep learning.

Although some pyroptosis-related (PR) prognostic models for cancers have been reported, pyroptosis-based features have not been fully discovered at the single-cell level in hepatocellular carcinoma (HCC). In this study, by deeply integrating single-cell and bulk transcriptome data, we systematically investigated significance of the shared pyroptotic signature at both single-cell and bulk levels in HCC prognosis. Based on the pyroptotic signature, a robust PR risk system was constructed to quantify the prognostic risk of individual patient. To further verify capacity of the pyroptotic signature on predicting patients' prognosis, an attention mechanism-based deep neural network classification model was constructed. The mechanisms of prognostic difference in the patients with distinct PR risk were dissected on tumor stemness, cancer pathways, transcriptional regulation, immune infiltration and cell communications. A nomogram model combining PR risk with clinicopathologic data was constructed to evaluate the prognosis of individual patients in clinic. The PR risk could also evaluate therapeutic response to neoadjuvant therapies in HCC patients. In conclusion, the constructed PR risk system enables a comprehensive assessment of tumor microenvironment characteristics, accurate prognosis prediction and rational therapeutic options in HCC.

Automatic Detection and Segmentation of Ovarian Cancer Using a Multitask Model in Pelvic CT Images.

Ovarian cancer is one of the most common malignant tumours of female reproductive organs in the world. The pelvic CT scan is a common examination method used for the screening of ovarian cancer, which shows the advantages in safety, efficiency, and providing high-resolution images. Recently, deep learning applications in medical imaging attract more and more attention in the research field of tumour diagnostics. However, due to the limited number of relevant datasets and reliable deep learning models, it remains a challenging problem to detect ovarian tumours on CT images. In this work, we first collected CT images of 223 ovarian cancer patients in the Affiliated Hospital of Qingdao University. A new end-to-end network based on YOLOv5 is proposed, namely, YOLO-OCv2 (ovarian cancer). We improved the previous work YOLO-OC firstly, including balanced mosaic data enhancement and decoupled detection head. Then, based on the detection model, a multitask model is proposed, which can simultaneously complete the detection and segmentation tasks.

Exosomal Non-Coding RNAs: New Insights into the Biology of Hepatocellular Carcinoma.

Exosomes, extracellular vesicles with a diameter of 40 to 160 nm, are among the smallest extracellular vesicles released by cells. They deliver different cargoes, including proteins, DNAs, and RNAs, and facilitate communication between cells to coordinate a variety of physiological and pathological functions. Hepatocellular carcinoma (HCC) is the sixth common malignant tumor and the fourth leading cause of cancer-related death worldwide. Its molecular mechanism remains largely unknown, and there is a lack of reliable and noninvasive biomarkers for early diagnosis and prognosis prediction. Mounting evidence has shown that exosomes carry a variety of ncRNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), which play critical roles in the occurrence and progression of HCC. In this review, we summarize the recent findings of exosomal miRNAs, lncRNAs, and circRNAs in HCC from their impact on the development of HCC to their potential applications in the diagnosis and treatment of HCC.

hsa_circ_0092339 acts as a molecular sponge in castration-resistant prostate cancer via the hsa-mir-940/C-MYC axis.

Aims: We aimed to determine whether intronic circRNA acts as a molecular sponge in castration-resistant prostate cancer (CRPC). Materials & methods: A gene chip technique was used to conduct sequencing. A qPCR experiment was performed to verify the result. Radioimmunoprecipitation, RNA pull-down and dual-luciferase reporter assays were performed to particularly expound its function. Verification of downstream effects was carried out through qPCR and western blot, and a xenograft assay was performed in vivo for verification. Results: Intronic circRNA hsa_circ_0092339 in the nucleus was highly expressed in CRPC cell lines. hsa_circ_0092339 did not regulate the expression of its parental gene. hsa_circ_0092339 functions like a molecular sponge, preventing degradation of C-MYC mRNA by absorbing hsa-mir-940. Conclusion: hsa_circ_0092339 plays a critical role in CRPC through targeting C-MYC indirectly by absorbing hsa-mir-940.

Our research breaks the mold by investigating a novel function of RNA and a novel regulatory mechanism. Our research provides a new therapeutic target for prostate cancer treatment and broadens the understanding of prostate cancer.

Multiresidue screening of pesticides in Panax Ginseng C. A. Meyer by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

In this study, an efficient screening method based on a modified quick, easy, cheap, effective, rugged, and safe extraction method combined with ultra-high-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry was established for the determination of 90 pesticides residues in Panax Ginseng. The accuracy of the method was then verified by analyzing the false positive rate and the screening detection limit in Ginseng. The results revealed that the screening detection limit of 33 of 90 pesticide residues were 0.01 mg·kg-1 , 22 species were 0.05 mg·kg-1 , 11 species were 0.10 mg·kg-1 , 8 species were 0.20 mg·kg-1 , and another 16 species were greater than 0.20 mg·kg-1 . A total of 73 pesticides were ultimately suitable to be practically applied for rapid analysis of pesticide residues in Ginseng. Finally, the established method was used to analyze the pesticide residues in 35 Ginseng samples available on the market. And the residual of dimethomorph, azoxystrobin, tebuconazole, and pyraclostrobin was relatively severe in Ginseng samples. This work expanded the range of pesticides detected and provided a rapid, effective method for pesticides screening in Ginseng.

A versatile insertion point on albumin to accommodate peptides and maintain their activities.

Genetic fusion of human serum albumin to peptides is an important strategy to enhance the plasma half-life of the peptide. An inherent challenge of such method is the reduction of specific activity of the cargo peptides upon connecting at N- or C-termini of albumin. Here, we report a finding that residue 363-364 of albumin can be inserted with a peptide while maintaining the peptide activities. We insert a peptide inhibitor into this site, and at the N-terminus of albumin, for comparison. The chimeric protein displays potent inhibition (IC50 value of 30 nM) to its target (uPAR), but not the N-terminally fused construct. We also study the chimera of HSA with a cyclic peptide inhibitor of murine urokinase-type plasminogen activator grafted at either the internal site or the N-terminus. The internally peptide-grafted protein possesses a much more potent inhibition compared to the N-terminally located fusion (IC50 value of 32 nM vs 19 µM). We further demonstrate that such internal fusion does not affect albumin expression, secondary structure, and inherent drug binding activity. Thus, this work identifies a versatile insertion point inside albumin for maintaining fusion peptide activity, and opens a new avenue to expand the applications of albumin fusion technology.

Downregulation of LOX promotes castration-resistant prostate cancer progression via IGFBP3.

The role of lysyl oxidase (LOX) in prostate cancer remains controversial. Studies have shown that LOX may inhibit the progression of prostate cancer (PCa), whereas other studies demonstrate that LOX may act as a tumor activator in PCa. Here, we report that low LOX expression contributes to CRPC progression through upregulation of IGFBP3. We showed that LOX expression decreased in the more advanced and aggressive castration-resistant prostate cancer (CRPC), compared to castration-sensitive prostate cancer (CSPC). We demonstrated that LOX was negatively correlated with IGFBP3 and may directly bind to the promoter of IGFBP3 and thus decrease the expression of IGFBP3. Inhibition of IGFBP3 by siRNA suppressed the growth and migration of CRPC cells, suggesting a critical role for IGFBP3 in CRPC. The preclinical study in a mouse model suggested that introducing back LOX inhibited the progression of CRPC. In summary, we identified a new function of LOX in PCa and discovered that LOX downregulation contributed to progression via IGFBP3, and that the restoration of LOX may be a promising therapeutic strategy for PCa.