The PFTK1 gene encodes a cdc2-related serine/threonine protein kinase that has been shown to confer cell migratory properties in hepatocellular carcinoma (HCC). However, the prognostic value and biological mechanism by which PFTK1 promotes HCC motility remain largely unknown. Here, we showed from tissue microarray that common upregulations of PFTK1 in primary HCC tumors (n=133/180) correlated significantly with early age onset (⩽40 years), advance tumor grading and presence of microvascular invasion (P⩽0.05). To understand downstream phosphorylated substrate(s) of PFTK1, phospho-proteins in PFTK1 expressing and knockdown Hep3B cells were profiled by two-dimensional-polyacrylamide gel electrophoresis mass spectrometric analysis. Protein identification of differential spots revealed β-actin (ACTB) and transgelin2 (TAGLN2) as the two most profound phosphorylated changes affected by PFTK1. We verified the presence of TAGLN2 serine phosphorylation and ACTB tyrosine phosphorylation. Moreover, reduced TAGLN2 and ACTB phosphorylations in PFTK1-suppressed Hep3B corresponded to distinct actin depolymerizations and marked inhibition on cell invasion and motility. Given that TAGLN2 is a tumor suppressor whose function has been ascribed in cancer metastasis, we examined if TAGLN2 is an intermediate substrate in the biological path of PFTK1. We showed in PFTK1-suppressed cells that knockdown of TAGLN2 over-rode the inhibitory effect on cell invasion and motility, and a recovery on actin polymerization was evident. Interestingly, we also found that unphosphorylated TAGLN2 in PFTK1-suppressed cells elicited strong actin-binding ability, a mechanism that possibly halts the actin cytoskeleton dynamics. Site-directed mutagenesis of TAGLN2 suggested that PFTK1 regulates the actin-binding affinity of TAGLN2 through the S83 and S163 residues, which if mutated can significantly affect HCC cell motility. Taken together, our data propose a novel, oncogene-tumor suppressor interplay, where oncogenic PFTK1 confers HCC cell motility through inactivating the actin-binding motile suppressing function of TAGLN2 via phosphorylation.

Understanding the sedentary patterns can guide the design of strategies to engage older adults in physical activity. This scoping review aimed to synthesize available evidence on sedentary behaviors in care facilities. We searched PubMed/MEDLINE and Web of Science for studies published from inception through October 2020. Eighteen studies were included and reviewed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Data obtained were analyzed based on levels of care provided. Overall, daily sedentary time was higher among residents in high level care facilities (e.g., nursing homes) (11.6 h/day) than intermediate/mixed level care facilities (e.g., assisted living) (9.5 h/day). In intermediate/mixed level care facilities, television (TV) viewing was the most common sedentary activity (2.5–2.9 h/day; 26% of daily sedentary time), while napping was the most favorite sedentary activity (4.7 h/day; 36% of waking hours) in high level care facilities. Sex differences in daily patterns of sedentary behavior (sedentary time, uninterrupted bouts, and bout durations) were commonly observed in intermediate/mixed level care facilities, as exemplified by men being more sedentary by 0.7–1.1 h/day. In summary, this study highlights distinctive sedentary patterns among older adults residing in different levels of care facilities, addressing a pressing need for customized interventions to engage care facility residents in physical activity.

Background: Mechanical loading is crucial for muscle and tendon tissue remodeling. Eccentric heel drop exercise has been proven to be effective in the management of Achilles tendinopathy, yet its induced change in the mechanical property (i.e., stiffness) of the Achilles tendon (AT), medial and lateral gastrocnemius muscles (MG and LG) was unknown. Given that shear wave elastography has emerged as a powerful tool in assessing soft tissue stiffness with promising intra- and inter-operator reliability, the objective of this study was hence to characterize the stiffness of the AT, MG and LG in response to an acute bout of eccentric heel drop exercise.Methods: Forty-five healthy young adults (36 males and nine females) performed 10 sets of 15-repetition heel drop exercise on their dominant leg with fully-extended knee, during which the AT and gastrocnemius muscles, but not soleus, were highly stretched. Before and immediately after the heel drop exercise, elastic moduli of the AT, MG and LG were measured by shear wave elastography.Results: After the heel drop exercise, the stiffness of AT increased significantly by 41.8 + 33.5% (P < 0.001), whereas the increases in the MG and LG stiffness were found to be more drastic by 75 + 47.7% (P < 0.001) and 71.7 + 51.8% (P < 0.001), respectively. Regarding the AT, MG and LG stiffness measurements, the inter-operator reliability was 0.940, 0.987 and 0.986, and the intra-operator reliability was 0.916 to 0.978, 0.801 to 0.961 and 0.889 to 0.985, respectively.Discussion: The gastrocnemius muscles were shown to bear larger mechanical loads than the AT during an acute bout of eccentric heel drop exercise. The findings from this pilot study shed some light on how and to what extent the AT and gastrocnemius muscles mechanically responds to an isolated set of heel drop exercise. Taken together, appropriate eccentric load might potentially benefit mechanical adaptations of the AT and gastrocnemius muscles in the rehabilitation of patients with Achilles tendinopathy.

Hepatocellular carcinoma (HCC) shows low response to most conventional chemotherapies. To facilitate target identification for novel therapeutic development, we deployed gene expression profiling on 43 paired HCC tumors and adjacent non-tumoral liver, which is also considered as the pre-malignant liver lesion. In conjunction with ontology analysis, a major functional process found to play a role in the malignant transformation of HCC was microtubule-related cellular assembly. We further examined the potential use of microtubule targeting taxane drugs, including paclitaxel and docetaxel, and compared with findings to results from doxorubicin, a common chemotherapeutic agent used in HCC. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, the nanoparticle albumin-bound (nab)-paclitaxel was also examined. In a panel of HCC cell lines studied, a high sensitivity towards taxane drugs was generally found, although the effect from nab-paclitaxel was most profound. The nab-paclitaxel showed an effective IC50 dose at 15-fold lower than paclitaxel alone or the derivative analogue docetaxel, and ~450-fold less compared to doxorubicin. Flow cytometric analysis confirmed a cell cycle blockade at the G2/M phase and increased apoptosis following nab-paclitaxel treatment. In vivo animal studies also showed that nab-paclitaxel readily inhibited xenograft growth with less toxicity to host cells compared to other anti-microtubule drugs and doxorubicin. Gene silencing of the microtubule regulatory gene STMN1 by RNAi suggested a distinct synergistic effect in the combined treatment with nab-paclitaxel. Our findings in this study highly suggest that the microtubule assembly represents a promising therapeutic target development in HCC.

Most women live with an inactive lifestyle, which suggests a need for preference-based choices to promote their participation in physical activity. This systematic review synthesized key findings on the health benefits of Qigong among women. We conducted a systematic search of randomized controlled trials (RCTs) of Qigong among women according to the PRISMA guidelines using the following databases from their inception through March 2021: PubMed/MEDLINE, Web of Science, Cochrane Library, and US National Library of Medicine. The risk of bias was examined using the Cochrane Collaborations tool for assessing the risk of bias in randomized trials. Altogether, 18 RCTs were included for final review. Results showed that Qigong was a feasible exercise in improving health outcomes, particularly depressive symptoms (63 of trials), quality of life (43), and fatigue (29), among general women, intimate partner violence survivors, and women with chronic conditions (e.g., breast cancer patients or survivors). Almost 90 (7/8) of trials reported high adherence rates ranging from 73 to 95 for supervised group training and 63 to 80 for home self-practice. Thus far, there was no evidence of serious adverse effects from performing Qigong. For the risk of bias across trials, a lack of allocation concealment (72 of trials), no blinding of participants and personnel (67), and incomplete outcome data (67) were the major sources. In summary, Qigong is a safe, feasible, and beneficial exercise for general women, abused sufferers, and health-compromised women. However, given the potential risk of bias found in many studies, improved rigor of study design in future trials will be imperatively required.