Multi-functional Chitosan Polymeric Micelles for improving the oral bioavailability of Paclitaxel based on synergistic effect.

A novel multi-functional micelle delivery system was developed for enhancing the oral absorption of paclitaxel (PTX). The delivery carriers were constructed by modifying chitosan-stearic acid (CS-SA) micelles with L-carnitine (LC) and co-encapsulating quercetin (Que), and the PTX-loaded micelles were prepared by film-sonication dispersing technique. The as-prepared micelles showed homogeneous spherical shapes with a small particle size of 148.3 ± 1.7 nm, high drug loading of 7.05% and low critical micelle concentration (CMC) of 16.89 µg/ml. Compared to the in-house PTX formulation similar to the commercial injection Taxol™, the target PTX-loaded micelles had obvious sustained-release effects and exhibited an oral relative bioavailability of 168.08%. The cellular uptake studies of Caco-2 cells confirmed the micellar modification of LC and the co-loading of Que played important roles in promoting the absorption of drug loaded in micelles. The CYP3A4 enzyme test demonstrated the micelles had an inhibitory effect on the metabolic enzyme due to the presence of Que. These findings confirmed the potential of the multi-functional chitosan polymeric micelles based on synergistic effect as an effective oral delivery system.

Self-improving dystrophic epidermolysis bullosa with a novel heterozygous missense variant in the COL7A1 gene in a Taiwanese family.

Self-improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self-improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self-improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases.

Serum cell division control 42 reflects treatment response and survival profiles in recurrent or metastatic oral squamous cell carcinoma patients who receive programmed death-1 inhibitors.

OBJECTIVES: Cell division control 42 (CDC42) facilitates tumor growth, migration, and immune escape to accelerate the pathogenesis and progression of oral squamous cell carcinoma (OSCC). This study intended to explore the optimal cut-value of serum CDC42 for predicting treatment response to programmed death-1 (PD-1) inhibitors and survival in recurrent or metastatic (R/M) OSCC patients. METHODS: CDC42 was detected from serum by enzyme-linked immunosorbent assay in 45 R/M OSCC patients before initiating PD-1 inhibitors with or without chemotherapy. Different cutoff values (500, 600, 700, and 800 pg/mL) of CDC42 were selected for further analyses. RESULTS: The median (interquartile range) value of CDC42 was 604.0 (477.5-867.5) pg/mL in R/M OSCC patients. Generally, objective response rate (ORR) and disease control rate (DCR) were 37.8 % and 62.2 %. Additionally, ORR (P = 0.030) and DCR (P = 0.004) were decreased in patients with CDC42 ≥ 700 pg/mL versus those with CDC42 < 700 pg/mL; meanwhile, DCR was also reduced in patients with CDC42 ≥ 800 pg/mL versus those with CDC42 < 800 pg/mL (P = 0.014). Interestingly, CDC42 ≥ 600 (P = 0.023), 700 (P = 0.007), and 800 (P = 0.039) pg/mL were related to shorter progression-free survival (PFS). While only CDC42 ≥ 700 (P = 0.004) and 800 (P = 0.046) pg/mL were correlated with worse overall survival (OS). After adjustment, only CDC42 ≥ 700 pg/mL (yes vs. no) independently estimated poor PFS (hazard ratio (HR) = 2.637, P = 0.005) and OS (HR = 5.824, P < 0.001). CONCLUSION: CDC42 ≥ 700 pg/mL exerts the optimal prognostic ability to reflect poor treatment response and survival profiles in R/M OSCC patients who receive PD-1 inhibitors.

Chaperonin containing TCP1 subunit 6A may activate Notch and Wnt pathways to facilitate the malignant behaviors and cancer stemness in oral squamous cell carcinoma.

Chaperonin containing TCP1 subunit 6A (CCT6A) was recently discovered to be involved in cancer pathogenesis and stemness; however, its role in oral squamous cell carcinoma (OSCC) has not been reported. The current study aimed to investigate the impact of CCT6A on OSCC cell malignant behaviors and stemness and to explore its potentially interreacted pathways. SCC-15 and HSC-3 cells were transfected with the plasmid loading control overexpression, CCT6A overexpression, control knockout, or CCT6A knockout. Wnt4 overexpression or Notch1 overexpression plasmids were transfected into CCT6A-knockout SCC-15 cells. Cell proliferation, apoptosis, invasion, stemness, Notch, and Wnt pathways were detected in both cell lines, whereas RNA sequencing was only performed in SCC-15 cells. CCT6A was upregulated in five OSCC cell lines, including SCC-15, HSC-3, SAT, SCC-9, and KON, compared to that in the control cell line. In SCC-15 and HSC-3 cells, CCT6A overexpression increased cell proliferation, invasion, sphere formation, CD133, and Sox2 expression, but decreased cell apoptosis; on the contrary, CCT6A knockout exhibited an opposite effect on the above indexes. RNA-sequencing data revealed that the Wnt and Notch pathways were involved in the CCT6A'effect on SCC-15 cell functions. CCT6A positively regulates the Wnt and Notch pathways in SCC-15 and HSC-3 cells. Importantly, it was shown that activation of the Wnt or Notch pathways attenuated the effect of CCT6A knockout on SCC-15 cell survival, invasion, and stemness. CCT6A may promote OSCC malignant behavior and stemness by activating the Wnt and Notch pathways.

Preparation of fluffy bimodal conjugated electrospun poly(lactic acid) air filters with low pressure drop.

Electrospun nanofiber membranes have been extensively studied as air filters. However, their limited filtration efficiency for submicron inhalable particulate matter (PM), high resistance to filtration, and limited capacity to hold dust have hindered their widespread use. The majority of materials come from petroleum, and the use of organic solvents during the spinning process has a significant negative impact on the environment. In this work, a sustainable method has been proposed for producing filters using poly(lactic acid) (PLA) with a bimodal diameter distribution through conjugated electrospinning. This technique allows for the continuous production of interconnected micro/nano hybrid porous membranes, resulting in reduced resistance and improved dust holding capacity. The filtration efficiency, pressure drop, long-term filtration performance, and actual performance of the conjugated bimodal membrane (CBM) were extensively investigated. The results indicate that the filter has a high capacity for retaining particles, with filtration efficiencies of 99.94% for PM 0.3 and 99.96% for PM 2.5. It also demonstrates a high quality factor (0.078 Pa-1 for PM 0.3 and 0.084 Pa-1 for PM 2.5), long-term stability (a decrease of 2.35% for PM 0.3 and 0.05% for PM 2.5 over a period of 60 days) and outstanding dust holding capacity (9.17 g m-2). The conjugated bimodal membrane (CBM) shows a 22.64% decrease in resistance compared to the non-conjugated bimodal membrane (BM). In general, the approach outlined in this work provides valuable insights into the development of high-performance biodegradable air filters. These filters have improved filtration efficiency and reduced resistance.

Investigation of the keratinocyte transcriptome altered in high-glucose environment: An in-vitro model system for precision medicine.

BACKGROUND: Impaired wound healing is a serious diabetes complication compromising patients' quality of life. However, the pathogenesis of diabetic wounds (DWs) remains incompletely understood. Human epidermal keratinocyte (HEK) is the sentinel cell that initiates healing processes after the epidermal integrity has been disrupted. OBJECTIVE: This study aimed to investigate the functional roles of HEKs in wound healing and to identify candidate genes, signaling pathways and molecular signatures contributing to the DWs. METHODS: HEKs were cultured in normal or high-glucose environment, followed by scratch, to mimic the microenvironment of normal wounds and DWs. Subsequently, we performed RNA sequencing and systematically analyzed the expression profiles by bioinformatics approaches. RESULTS: High-glucose environment altered the keratinocyte transcriptome responses to wounding. In experimental model of DWs, we found that TNF, CYP24A1, NR4A3 and GGT1 were key overexpressed genes in keratinocytes and were implicated in multiple cellular responses. Further analysis showed that wounding in high-glucose environment activated G-protein-coupled receptor (GPCR) signaling, cAMP response element-binding protein (CREB) signaling, and adrenomedullin signaling in keratinocytes, while dysregulated skin development and immune responses as compared to their counterpart in normal glucose settings. CONCLUSION: This simplified in-vitro model serves as a valuable tool to gain insights into the molecular basis of DWs and to facilitate establishment of personalized therapies in clinical practice.

Lumbar paraspinal atypical spindle cell/pleomorphic lipomatous tumor: A report of a rare case.

The atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) was classified as a new tumor by the World Health Organization (WHO) in 2020. The tumor is benign and commonly occurs in the limbs. Paraspinal presentations are rare. A 38-year-old man presented at our clinic complaining of sudden onset back pain. No neurological deficit was found. The magnetic resonance imaging (MRI) revealed a well-defined heterogeneous mass in the left psoas muscle, from L1 to L3 extending over the L1 and L2 neuroforamen. The tumor was totally excised. Pathology led to an ASPLT diagnosis. Clinical symptoms improved and there was no postsurgical neurological deficit. This case of ASPLT, located in an uncommon location and present an unusual cluster of symptoms, could be treated by surgical excision, usually the first-treatment strategy. Totally, removal was achieved because there was a clear morphological margin. The risk of metastatic dissemination was minimal, though there remains a nonnegligible risk of local recurrence.

Air-mattress system for ballistocardiogram-based heart rate and breathing rate estimation.

Sleep-related problems are widespread. Numerous devices for sleep monitoring are increasingly available, including smartwatches, sleep monitoring rings, etc. These devices accumulate and analyze a substantial quantity of physiological data. In this study, we develop a smart air-mattress system that can effectively aid health measurements. The proposed system adopts an air-mattress system to detect subtle changes in pressure and thereby collect micro physiological signals, including ballistocardiography (BCG) and breathing signals. The system uses ultrasonic signals to detect the subject's turning movements. To increase the signal recognition accuracy, the BCG signal is processed effectively to reduce noise interference engendered by the body movement during sleep and is processed using regression analysis for heart rate and breathing rate estimation. Accordingly, the proposed system is unconstrained and can be used to collect micro BCG signals, breathing signals, heart rate signals, and turning movements for the long-term health-care.

High expression of NLRP12 predicts poor prognosis in patients with intracranial glioma.

BACKGROUND: Intracranial gliomas are the most common primary central nervous system tumors in humans, and glioblastoma multiforme is the most malignant intracranial glioma. The nucleotide-binding domain leucine-rich repeat (NLR)-containing family are crucial regulators of inflammatory and innate immune responses. NLRP12 codes for the monarch-1 protein, which regulates immune responses in humans. Data from a next-generation sequencing database indicated that NLRP12 expression is increased in glioma cells. However, the relationship between NLRP12 levels and gliomas is unclear. METHODS: To explore the role of NLRP12-related translation factors and proteins in glioma, we evaluated the clinical data and paraffin sections from glioma patients. The expression of NLRP12 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests. RESULTS: The degree of malignancy and prognosis highly correlated with NLRP12 levels. In addition, the siRNA-mediated downregulation of NLRP12 in glioma cell lines decreased proliferation, invasion, and migration. The levels of VEGF, N-cadherin, and cyclin D1 were downregulated after knockdown of NRLP12 in glioma cell lines, as observed using western blotting in vitro. Knockdown of NLRP12 attenuated the tumor progression in vivo. CONCLUSION: The expression of NLRP12 may be an independent prognostic factor and a potential target for the treatment of intracranial glioma.

Linolenic acid conjugated chitosan micelles for improving the oral absorption of doxorubicin via fatty acid transporter.

A novel delivery system based on linolenic acid (LA) conjugated chitosan (CS) polymeric micelles were proposed for improving the oral absorption of doxorubicin (DOX) through targeting intestinal fatty acid transporter. LA, as a ligand of the transporter, was grafted into CS to construct CS-LA micelles, and DOX was encapsulated into the micelles. The synthesized micelle material was identified by 1H NMR and FT-IR. The micelles showed regular spherical shapes with a particle size of 117.1 ± 1.6 nm, drug loading of 8.77 ± 0.02 %, and critical micelle concentration (CMC) of 23.6 µg/ml. The pharmacokinetics studies showed the relative bioavailability of 166 % versus DOX·HCl. The fatty acid transport protein 4-mediated intestinal uptake process of micelles was confirmed by the intracellular uptake, immunofluorescent imaging and permeation test. These findings confirmed the potential of CS-LA micelles as an effective oral delivery vehicle, and fatty acid transporter as a target spot for enhancing intestinal drug absorption.

Relationship Between Physical Performance and Peripheral Arterial Diseases in Different Age Groups of Chinese Community-Dwelling Older Adults.

AIMS: This study aimed to examine the relationship between physical performance and peripheral artery disease (PAD) in different age groups of Chinese older adults. METHODS: We enrolled 1357 relatively healthy ≥ 65 years old participants of Chinese ethnicity. We classified the participants into two age categories, the pre-old group (65-74 years, n=968) and the old group (≥ 75 years, n=389). We assessed the cross-sectional association of the ankle-brachial index (ABI), which is used for the classification of patients with PAD (ABI ≤ 0.9). Physical performance mainly focused on muscle strength, mobility, and balance, which were measured via hand grip, 4 m walking speed, and the Timed Up and Go Test. RESULTS: A total of 125 (9.2%) patients met the diagnostic criteria and were defined as having PAD. After multivariate adjustment, we found that grip strength and 4 m walking speed were correlated negatively with PAD (odds ratio (OR)=0.953, 95% confidence interval (CI)=0.919-0.989; OR=0.296, 95% CI=0.093-0.945) in pre-old participants, whereas balance (OR=1.058, 95% CI=1.007-1.112) was correlated positively with PAD only in older participants. CONCLUSION: Our study further confirmed the association between physical performance and PAD in community-dwelling older Chinese adults. Muscle strength and mobility correlated negatively with PAD, and balance was positively associated with PAD in older participants. These findings might help with better early screening and management of PAD.

Extraction of pigments from camellia seed husks and their application on silk fabrics.

To reuse camellia husk waste and expand the scope of natural dyes, this research proposes pigment extraction from camellia husks and investigates various properties when applied on silk fabrics. Single-factor experiments were used to screen and optimize the dyeing process. The extracted pigments and dyed fibers were analyzed and characterized by LC-MS, FTIR and SEM, respectively. Six metal mordants were compared with each other, and their possible mordanting mechanisms were proposed. Color fastness, UV resistance, and antioxidant and antibacterial properties were evaluated after dyeing. The results showed that the optimal dyeing process was as follows: dyestuff mass 50 g L-1, holding time 45 min, bath pH 3.0, holding temperature 100 °C. LC-MS and FTIR results showed that the pigments in the extracts were mainly dimeric and multimeric procyanidins. Metal ion addition increased the K/S value while the pre-mordanting method had a superior dyeing depth. The rubbing and washing fastness of the dyed fabric were all above grade 4.0. Meanwhile, the dyed sample exhibited favorable UV resistance, and antioxidant and antibacterial properties, including a UPF index of 63.4 and an inhibition rate of 98.74% and 97.39% for S. aureus and E. coli, respectively.

High expression of GSKIP is associated with poor prognosis in meningioma.

Meningiomas are the most common extra-axial primary central nervous system tumors. There is no effective treatment or targeted therapy for meningioma except excision and radiotherapy. glycogen synthesis kinase 3ß interaction protein (GSKIP) is an A-kinase anchor protein that has cytosolic scaffolding function and binds to a protein kinase A and glycogen synthesis kinase 3ß to modulate different biological processes and malignant tumorigenesis through the Wnt pathway. The purpose of this study was to investigate the relationship between GSKIP expression and the clinico-pathological parameters in meningioma using immunohistochemical staining. We collected samples from 74 patients, from 2008 to 2012, in the Kaohsiung Medical University Hospital that had data on the staging and prognosis of the meningioma pathological section. Chi-square, Kaplan-Meier method, and cox regression were used to analyze the correlation between clinical parameters and immunohistochemistry staining for GSKIP. Following our immunohistochemical score, we found that higher expression of GSKIP was associated with high World Health Organization grading, recurrence, malignant transformation, and reduced overall survival time and recurrence-free survival time in meningioma. GSKIP may be a biomarker of poor prognosis and a target protein for therapy in meningioma.

[A consensus on prenatal diagnosis and genetic counseling for chromosomal mosaicism].

With the extensive application of highly sensitive genetic techniques in the field of prenatal diagnosis, prenatal chromosomal mosaicisms including true fetal mosaicisms and confined placental mosaicisms are frequently identified in clinical settings, and the diagnostic criteria and principle of genetic counseling and clinical management for such cases may vary significantly among healthcare centers across the country. This not only has brought challenges to laboratory technician, genetic counselor and fetal medicine doctor, but can also cause confusion and anxiety of the pregnant woman and their family members. In this regard, we have formulated a consensus over the prenatal diagnosis and genetic counseling for chromosomal mosaicisms with the aim to promote more accurate and rational evaluation for fetal chromosomal mosaicisms in prenatal clinics.

Both Short and Long Sleep Durations are Risk Factors for Sarcopenia in Suburban-Dwelling Older Chinese Individuals: A 3-Year Longitudinal Study.

Background: Few longitudinal studies have explored exploring the relationship between sleep duration and sarcopenia. Evidence concerning the relationship between sleep duration and sarcopenia is limited and inconsistent. The purpose of this 3-year prospective study was to explore whether sleep duration was associated with sarcopenia onset in suburb-dwelling older Chinese individuals. Methods: This was a prospective study that included 754 Chinese suburb-dwelling men and women aged ≥60 years (men n=327, mean age 65.24± 4.87 years) who were not initially diagnosed with sarcopenia. We defined sarcopenia using the diagnostic algorithm recommended by the Asian Working Group for Sarcopenia. Self-reported sleep duration was a component of the interview measured by trained interviewers. Subjects were categorized into 3 groups at baseline [short: <6 h, medium: 6-8 h, and long: >8 h]. Results: The incidence of sarcopenia during the 3-year follow-up was 12.2%. Multivariate logistic regression analyses showed that after adjustments for potential confounders long sleep duration was independently associated with sarcopenia incidence from baseline through the 3-year follow-up: when using the 6-8 h sleep duration group as a reference, the adjusted ORs for sarcopenia of the groups who slept <6 and >8 hours were 2.74 (95% CI 1.05-7.13) and 1.84 (95% CI 1.07-3.14). Conclusion: Both short and long sleep durations were associated with a greater incidence of sarcopenia. Thus, sleep duration should be considered when developing prevention and management strategies for sarcopenia.