Therapeutic effects of green tea on endometriosis.

Endometriosis is a chronic disorder characterized by the presence of endometrial glands and stroma outside the uterine cavity. It affects 8%-10% of women in their reproductive years, and represents a major clinical problem with deleterious social, sexual and reproductive consequences. Current treatment options include pain relief, hormonal intervention and surgical removal. However, these treatments are deemed unsatisfactory owing to varying success, significant side effects and high recurrence rates. Green tea and its major bioactive component, (-)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly anti-angiogenic, anti-proliferation, anti-metastasis, and apoptosis induction. In recent years, preclinical studies have proposed the use of green tea to inhibit the growth of endometriosis. Herein, the aim of this review is to summarize the potential therapeutic effects of green tea on molecular and cellular mechanism through inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis in endometriosis.

Morphological changes of Intervertebral Disc detectable by T2-weighted MRI and its correlation with curve severity in Adolescent Idiopathic Scoliosis.

BACKGROUND: Our previous studies found disproportionate anteroposterior vertebral size is associated with severity of the scoliotic curves in adolescent idiopathic scoliosis (AIS) patients. Subsequent studies showed wedging of vertebral bodies (VB) had less contribution than intervertebral discs (IVD) to the anterior-posterior vertebral column length discrepancy in severe-AIS. However, the exact morphological changes of IVD were not clearly defined. This study aimed to evaluate the morphological and pathological changes of IVD and VB in AIS girls and healthy female controls. METHODS: This study included 33 age-matched female controls and 76 AIS girls with a right-sided thoracic curvature. Wedge angle, height ratio and distance ratio of VB and IVD were measured on the best midline coronal and sagittal planes from reformatted MRI spine. Volumes of VB, IVD and nucleus pulposus (NP) were also evaluated on volumetric images. One-way ANOVA with Bonferroni correction and Pearson correlation tests were used. RESULTS: There was significant difference in wedge angle and height ratio of VB and IVD between AIS and controls. In severe-AIS, the position of NP was significantly shifted to the convexity when compared with non-severe AIS and controls. Whereas, the volume of IVD and NP in severe-AIS was found to be significantly smaller. In addition, Cobb angle was significantly correlated with wedge angle and height ratio, and inversely correlated with the volume of NP. CONCLUSIONS: In addition to wedging of VB and IVD, there was significantly reduced volume of IVD and NP in AIS patients with severe curve, insinuating the mechanical effect of scoliosis leads to a compression on both IVD and NP before significant disc desiccation occurs. We postulate that the compression of IVD and NP can contribute to curve progression in severe-AIS, these patients are more prone to disc degeneration in adulthood if no operative treatment is offered. Further longitudinal study on these parameters is still warranted.

Large lateral tibial slope and lateral-to-medial slope difference are risk factors for poorer clinical outcomes after posterolateral meniscus root tear repair in anterior cruciate ligament reconstruction.

BACKGROUND: Meniscus root tear is an uncommon but detrimental injury of the knee. Hoop stress is lost during meniscus root tear, which can lead to excessive tibiofemoral contact pressure and early development of osteoarthritis. Posterolateral meniscus root tears (PLRT) are more commonly associated with anterior cruciate ligament (ACL) tears. As the lateral compartment is less congruent than the medial compartment, it is more susceptible to a shearing force, which is increased in the ACL-deficient knee. In accordance with the compressive axial load, the increase in the tibial slope would generate a greater shearing force. The additional lateral compartment mobility caused by ACL tear should be reduced after ACL reconstruction (ACLR). However, there is a lack of evidence to conclude that ACLR can sufficiently limit the effect of large tibial slope (LTS) on the healing after PLRT repair. This study aimed to evaluate whether a steep LTS would be a risk factor for poorer clinical outcomes after PLRT repair concomitant with ACLR. METHODS: In this retrospective study, a chart review was conducted to identify patients with concomitant unilateral primary ACLR and PLRT repair. Patients with a partial tear or healed tear were excluded. Postoperative MRI and clinical assessments were performed at a mean follow up of 35 months. MRI data was used to measure the LTS, medial tibial slope (MTS), coronal tibial slope (CTS), the lateral-to-medial slope difference (LTS-MTS) and meniscus healing and extrusion. Functional outcomes were evaluated by patient-reported outcomes (International Knee Documentation Committee [IKDC], Lysholm and Tegner scores) and KT-1000 arthrometer assessment. Interobserver reproducibility was assessed by two reviewers. RESULTS: Twenty-five patients were identified for the analysis. Patients with larger LTS and larger LTS-MTS differences were shown to be correlated with poorer IKDC scores after surgery (R = -0.472, p = 0.017 and R = -0.429, p = 0.032, respectively). Herein, patients with LTS ≥ 6° or LTS-MTS ≥ 3° demonstrated poorer IKDC scores. CONCLUSION: A large LTS (≥ 6°) and a large difference of LTS-MTS (≥ 3°) were shown to be risk factors for poorer functional and radiological outcomes for PLRT repair in patients after ACLR. Clinically, closer monitoring and a more stringent rehabilitation plan for patients with LTS ≥ 6° or LTS-MTS ≥ 3° would be recommended.

Global sagittal alignment of the spine, pelvis, lower limb after vertebral compression fracture and its effect on quality of life.

BACKGROUND: Vertebral compression fractures (VCFs) are the most common among all osteoporotic fractures. The body may compensate to the kyphosis from vertebral compression fractures with lordosis of the adjacent spinal segments, rotation of the pelvis, knee flexion and ankle dorsiflexion. However, the detailed degree of body compensation, especially the lower limb, remains uncertain. Herein, the aim of this study is to investigate the values of global sagittal alignments (GSA) parameters, including the spine, pelvis and lower limbs, in patients with and without VCFs, as well as to evaluate the effect of VCFs on various quality of life (QoL) parameters. METHODS: A cross-sectional study was conducted from May 2015 to June 2018. A total of 142 patients with VCFs aged over 60 years old and 108 age-matched asymptomatic controls were recruited. Whole body sagittal alignment including thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), T1-pelvic angle (TPA), knee-flex angle (KA) and ankle-flex angle (AA) were measured. In addition, lower back pain and quality of life were assessed using self-reported questionnaires. RESULTS: Compared to asymptomatic controls, patients with VCF showed significantly greater TK (33.4o ± 16.4o vs 28.4o ± 11.4o; p < 0.01), PT (25.4o ± 10.5o vs 16.6o ± 8.9o; p < 0.001), PI (54.6o ± 11.8o vs 45.8o ± 12.0o; p < 0.001), SVA (49.1 mm ± 39.6 mm vs 31.5 mm ± 29.3 mm; p < 0.01), and TPA (28.6o ± 10.8o vs 14.8o ± 8.6o; p < 0.001). Whereas for lower limb alignment, patients with VCF showed significantly higher KA (10.1o ± 7.8o vs 6.0o ± 6.4o; p < 0.001) and AA (7.0o ± 3.9o vs 4.8o ± 3.6o; p < 0.001) than controls. The number of VCF significantly correlated with lower limb alignments (KA and AA) and global sagittal balance (TPA). VCF patients showed poorer quality of life assessment scores in terms of SF-12 (30.0 ± 8.3 vs 72.4 ± 16.9; p < 0.001), ODI (37.8 ± 24.0 vs 18.7 ± 16.6; p < 0.001) and VAS (3.8 ± 2.8 vs 1.9 ± 2.2; p < 0.001). CONCLUSION: This is the first study to illustrate the abnormal lower limb alignment exhibited in patients with VCF. Patients with VCF showed an overall worse global sagittal alignment and decreased quality of life. Poorer global sagittal alignment of VCF patients also imply worse quality of life and more severe VCF.

Therapeutic potential of a novel prodrug of green tea extract in induction of apoptosis via ERK/JNK and Akt signaling pathway in human endometrial cancer.

BACKGROUND: Previous studies have shown a major green tea polyphenol (-)-epigallocatechin-3-gallate ((-)-EGCG) as a powerful anti-cancer agent. However, its poor bioavailability and requirement of a high dosage to manifest activity have restricted its clinical application. Recently, our team synthesized a peracetate-protected derivative of EGCG, which can act as a prodrug of (-)-EGCG (ProEGCG) with enhanced stability and improved bioavailability in vitro and in vivo. Herein, we tested the therapeutic efficacy of this novel ProEGCG, in comparison to EGCG, toward human endometrial cancer (EC). METHODS: In this study, the effects of ProEGCG and EGCG treatments on cell growth, cell survival and modulation of intracellular signaling pathways in RL95-2 and AN3 CA EC cells were compared. The antiproliferative effect was evaluated by cell viability assay. Apoptosis was measured by annexin/propidium iodide staining. Expression of mitogen-activated protein kinases, markers of proliferation and apoptosis were measured by immunoblot analysis. In addition, the effects of ProEGCG and EGCG on tumor growth, vessel formation and gene expression profiles on xenograft models of the EC cells were investigated. RESULTS: We found that treatment with ProEGCG, but not EGCG, inhibited, in a time- and dose-dependent manner, the proliferation and increased apoptosis of EC cells. Treatment with low-dose ProEGCG significantly enhanced phosphorylation of JNK and p38 MAPK and inhibited phosphorylation of Akt and ERK which are critical mediators of apoptosis. ProEGCG, but not EGCG, elicited a significant decrease in the growth of the EC xenografts, promoted apoptotic activity of tumour cells in the EC xenografts, and decreased microvessel formation, by differentially suppressing anti-apoptotic molecules, NOD1 and NAIP. Notably, no obvious adverse effects were detected. CONCLUSIONS: Taken together, ProEGCG at a low dose exhibited anticancer activity in EC cells through its anti-proliferative, pro-apoptotic and anti-tumor actions on endometrial cancer in vitro and in vivo. In contrast, a low dose of EGCG did not bring about similar effects. Importantly, our data demonstrated the efficacy and safety of ProEGCG which manifests the potential of a novel anticancer agent for the management of endometrial cancer.

Mushroom extracts and compounds with suppressive action on breast cancer: evidence from studies using cultured cancer cells, tumor-bearing animals, and clinical trials.

This article reviews mushrooms with anti-breast cancer activity. The mushrooms covered which are better known include the following: button mushroom Agaricus bisporus, Brazilian mushroom Agaricus blazei, Amauroderma rugosum, stout camphor fungus Antrodia camphorata, Jew's ear (black) fungus or black wood ear fungus Auricularia auricula-judae, reishi mushroom or Lingzhi Ganoderma lucidum, Ganoderma sinense, maitake mushroom or sheep's head mushroom Grifola frondosa, lion's mane mushroom or monkey head mushroom Hericium erinaceum, brown beech mushroom Hypsizigus marmoreus, sulfur polypore mushroom Laetiporus sulphureus, Lentinula edodes (shiitake mushroom), Phellinus linteus (Japanese "meshimakobu," Chinese "song gen," Korean "sanghwang," American "black hoof mushroom"), abalone mushroom Pleurotus abalonus, king oyster mushroom Pleurotus eryngii, oyster mushroom Pleurotus ostreatus, tuckahoe or Fu Ling Poria cocos, and split gill mushroom Schizophyllum commune. Antineoplastic effectiveness in human clinical trials and mechanism of anticancer action have been reported for Antrodia camphorata, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes.

New ribosome-inactivating proteins and other proteins with protein synthesis-inhibiting activities.

Ribosome-inactivating proteins (RIPs) consist of three varieties. Type 1 RIPs are single-chained and approximately 30-kDa in molecular weight. Type 2 RIPs are double-chained and composed of a type 1 RIP chain and a lectin chain. Type III RIPs, such as maize b-32 barley and JIP60 which are produced as single-domain proenzymes, possess an N-terminal domain corresponding to the A domain of RIPs and fused to a C-terminal domain. In addition to the aforementioned three types of RIPs originating from flowering plants, there are recently discovered proteins and peptides with ribosome-inactivating and protein synthesis inhibitory activities but which are endowed with characteristics such as molecular weights distinctive from those of the regular RIPs. These new/unusual RIPs discussed in the present review encompass metazoan RIPs from Anopheles and Culex mosquitos, antimicrobial peptides derived from RIP of the pokeweed Phytolacca dioica, maize RIP (a type III RIP derived from a precursor form), RIPs from the garden pea and the kelp. In addition, RIPs with a molecular weight smaller than those of regular type 1 RIPs are produced by plants in the Cucurbitaceae family including the bitter gourd, bottle gourd, sponge gourd, ridge gourd, wax gourd, hairy gourd, pumpkin, and Chinese cucumber. A small type II RIP from camphor tree (Cinnamomum camphora) seeds and a snake gourd type II RIP with its catalytic chain cleaved into two have been reported. RIPs produced from mushrooms including the golden needle mushroom, king tuber mushroom, straw mushroom, and puffball mushroom are also discussed in addition to a type II RIP from the mushroom Polyporus umbellatus. Bacterial (Spiroplasma) RIPs associated with the fruitfly, Shiga toxin, and Streptomyces coelicolor RIP are also dealt with. The aforementioned proteins display a diversity of molecular weights, amino acid sequences, and mechanisms of action. Some of them are endowed with exploitable antipathogenic activities.

Accuracy on the preoperative assessment of patients with adolescent idiopathic scoliosis using biplanar low-dose stereoradiography: a comparison with computed tomography.

BACKGROUND: Although computed tomography (CT) is commonly used to diagnose the scoliotic spine in patients with adolescent idiopathic scoliosis (AIS) preoperatively, it is limited by the high radiation and prone scanning position. Recently, a new biplanar stereoradiography (EOS) was used to image the scoliotic spine in an upright posture with significantly less radiation in non-severe AIS subjects. However, its reliability to assess preoperative AIS patients remains unreported. Hence, the purpose of this study is to compare the scoliotic curvature between prone (CT) and upright positions (EOS) in preoperative AIS patients. METHODS: Thirty-three pre-operative AIS patients (mean age:18.4 ± 4.2) were recruited. EOS was used to scan the whole thoracic spine at upright position. Whereas on the same day, a conventional CT scan was used to evaluate the spine in prone position. The three-dimensional reconstruction of EOS and CT of the spine were then generated. Using previous validated techniques, multiple scoliotic parameters in both modalities were determined. The agreement between the two modalities was compared using the Bland-Altman test, whereas the correlation was assessed by the intraclass correlation coefficient (ICC). RESULTS: The mean ICC (prone and upright) of intra-rater/inter-rater reliabilities for the measured parameters were 0.985,0.961/0.969,0.903, respectively. Thoracic Cobb angles, intervertebral wedging and lumbar lordosis correlated significantly between upright EOS imaging radiographs (62.9 ± 9.3°,6.4 ± 2.9° and 48.8 ± 12.4°) and prone CT (47.3 ± 10.0°,5.8 ± 2.7° and 27.9 ± 11.4°; P < 0.001). The apical vertebral wedging and apical intervertebral disc wedging showed a good correlation among the two modalities (upright, 6.5 ± 3.5° and 6.4 ± 2.9°; prone, 6.5 ± 3.6° and 5.8 ± 2.7°; R2 ≥ 0.94; P < 0.01). Similarly, there was significant correlation in apical intervertebral rotation (R2 = 0.834; P < 0.01) between the prone CT (3.4 ± 3.0°) and upright EOS (3.8 ± 3.2°). In addition, the Cobb angle was significantly larger in upright EOS (62.9 ± 9.3°) than in prone CT (47.3 ± 10.0°, P < 0.01) position. There was significant underestimation on scoliotic severity in the prone position when compared with upright position. CONCLUSIONS: Importantly, the image acquisition and reconstruction from EOS can better provide accurate three-dimensional spinal representations of the scoliotic curvature in preoperative AIS patients. Moreover, our findings suggested that scoliotic curvatures in preoperative AIS patients can be largely represented by both imaging modalities despite the difference in body positioning.

MDSCs drive the process of endometriosis by enhancing angiogenesis and are a new potential therapeutic target.

Endometriosis affects women of reproductive age via unclear immunological mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, we found MDSCs significantly increased in the peripheral blood of patients with endometriosis and in the peritoneal cavity of a mouse model of surgically induced endometriosis. Majority of MDSCs were granulocytic, produced ROS, and arginase, and suppressed T-cell proliferation. Depletion of MDSCs by antiGr-1 antibody dramatically suppressed development of endometrial lesions in mice. The chemokines CXCL1, 2, and 5 were expressed at sites of lesion while MDSCs expressed CXCR-2. These CXC-chemokines promoted MDSC migration toward endometriotic implants both in vitro and in vivo. Also, CXCR2-deficient mice show significantly decreased MDSC induction, endometrial lesions, and angiogenesis. Importantly, adoptive transfer of MDSCs into CXCR2-KO mice restored endometriotic growth and angiogenesis. Together, this study demonstrates that MDSCs play a role in the pathogenesis of endometriosis and identifies a novel CXC-chemokine and receptor for the recruitment of MDSCs, thereby providing a potential target for endometriosis treatment.

Clinicopathological and prognostic significance of blood microvessel density in endometrial cancer: a meta-analysis and subgroup analysis.

OBJECTIVE: The study aimed to systematically review the association between angiogenesis and clinicopathological characteristics and its prognostic value in patients with endometrial cancer. METHODS: Eligible studies were searched in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang database. Studies that assessed blood microvessel density (BMVD) and correlated with clinicopathological features and/or overall survival (OS) were included. Geometric mean values and hazard ratio with 95% confidence interval were pooled to examine the risk or hazard association. Subgroup analyses were conducted based on populations, BMVD criteria, BMVD markers, and type of survival analysis. RESULTS: A total of 29 studies of 2517 patients were included. BMVD was associated with depth of myometrial invasion (MI) [standard mean difference (SMD) 1.24; 95% CI 0.53-1.95; P = 0.0006], lymphovascular space invasion (LVSI) (SMD 0.75; 95% CI 0.3-1.21; P = 0.001), and lymph node metastasis (LNM) (SMD 0.99; 95% CI 0.46-1.52; P = 0.0003). BMVD was also significantly associated with poor OS (HR 2.65; 95% CI 1.86-3.77; P < 0.00001). The association remained significant in the subgroups Asian population, BMVD criteria using Weidner method, BMVD marker CD34 for MI, LVSI, and LNM, CD105 for MI, and factor VIII for MI and LNM, respectively. For OS, either Asian or non-Asian population, BMVD criteria using Weidner or non-Weidner method, BMVD marker CD31, or factor VIII antibody and analysis using univariate or multivariate were all significantly associated. CONCLUSIONS: BMVD was associated with deeper MI, positive LVSI, positive LNM, and poor OS in patients with endometrial cancer. Therefore, angiogenesis is a useful measure for poor clinicopathological outcomes and prognosis in patients with endometrial cancer.

Serotonin receptor 6 mediates defective brain development in monoamine oxidase A-deficient mouse embryos.

Monoamine oxidases A and B (MAO-A and MAO-B) are enzymes of the outer mitochondrial membrane that metabolize biogenic amines. In the adult central nervous system, MAOs have important functions for neurotransmitter homeostasis. Expression of MAO isoforms has been detected in the developing embryo. However, suppression of MAO-B does not induce developmental alterations. In contrast, targeted inhibition and knockdown of MAO-A expression (E7.5-E10.5) caused structural abnormalities in the brain. Here we explored the molecular mechanisms underlying defective brain development induced by MAO-A knockdown during in vitro embryogenesis. The developmental alterations were paralleled by diminished apoptotic activity in the affected neuronal structures. Moreover, dysfunctional MAO-A expression led to elevated levels of embryonic serotonin (5-hydroxytryptamine (5-HT)), and we found that knockdown of serotonin receptor-6 (5-Htr6) expression or pharmacologic inhibition of 5-Htr6 activity rescued the MAO-A knockdown phenotype and restored apoptotic activity in the developing brain. Our data suggest that excessive 5-Htr6 activation reduces activation of caspase-3 and -9 of the intrinsic apoptotic pathway and enhances expression of antiapoptotic proteins Bcl-2 and Bcl-XL. Moreover, we found that elevated 5-HT levels in MAO-A knockdown embryos coincided with an enhanced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and a reduction of proliferating cell numbers. In summary, our findings suggest that excessive 5-HT in MAO-A-deficient mouse embryos triggers cellular signaling cascades via 5-Htr6, which suppresses developmental apoptosis in the brain and thus induces developmental retardations.

Correction: wai, m.g.C., et Al. A review of pinealectomy-induced melatonin-deficient animal models for the study of etiopathogenesis of adolescent idiopathic scoliosis. Int. J. Mol. Sci. 2014, 15, 16484-16499.

The authors wish to make the following corrections to this paper [1]: The first name and surname of the authors were reversed. It should be corrected in the following format (with the surname in bold text):[...].

Determination of exogenous epigallocatechin gallate peracetate in mouse plasma using liquid chromatography with quadrupole time-of-flight mass spectrometry.

A robust method for the quantitation of epigallocatechin gallate peracetate in plasma for pharmacokinetic studies is lacking. We have developed a validated method to quantify this compound using liquid chromatography with quadrupole time-of-flight mass spectrometry with isopropanol and tert-butyl methyl ether (3:10) extraction and thin-layer chromatography purification. The epigallocatechin gallate peracetate-1-(13) C8 isotope was used as an internal standard. The linear range (r(2) > 0.9950) was from 0.05 to 100.00 µg/mL. The lower limit of quantification of the method was 0.05 µg/mL. Reproducibility, coefficient of variation, was between 0.7 and 12.6% (n = 6), accuracy between 83.7 and 104.6% (n = 5), and recovery ranged from 82.4 to 109.0% (n = 4). Ion suppression was approximately 40%. No mass spectral peaks were found to interfere between the standard and internal standard or the blank plasma extracts. Epigallocatechin gallate peracetate in plasma was stably stored at -80°C over three months even after three freeze-thaw cycles. Extracts were stable in the sampler at 4°C for over 48 h. Plasma levels were maintained at 1.36 µg/mL for 360 min after intraorbital intravenous injection at 50 mg/kg in mice. This method can be used to reliably measure epigallocatechin gallate peracetate in plasma for pharmacokinetic studies.

Abnormal response of the proliferation and differentiation of growth plate chondrocytes to melatonin in adolescent idiopathic scoliosis.

Abnormalities in the melatonin signaling pathway and the involvement of melatonin receptor MT2 have been reported in patients with adolescent idiopathic scoliosis (AIS). Whether these abnormalities were involved in the systemic abnormal skeletal growth in AIS during the peripubertal period remain unknown. In this cross-sectional case-control study, growth plate chondrocytes (GPCs) were cultured from twenty AIS and ten normal control subjects. Although the MT2 receptor was identified in GPCs from both AIS and controls, its mRNA expression was significantly lower in AIS patients than the controls. GPCs were cultured in the presence of either the vehicle or various concentrations of melatonin, with or without the selective MT2 melatonin receptor antagonist 4-P-PDOT (10 µM). Then the cell viability and the mRNA expression of collagen type X (COLX) and alkaline phosphatase (ALP) were assessed by MTT and qPCR, respectively. In the control GPCs, melatonin at the concentrations of 1, 100 nM and 10 µM significantly reduced the population of viable cells, and the mRNA level of COLX and ALP compared to the vehicle. Similar changes were not observed in the presence of 4-P-PDOT. Further, neither proliferation nor differentiation of GPCs from AIS patients was affected by the melatonin treatment. These findings support the presence of a functional abnormality of the melatonin signaling pathway in AIS GPCs, which might be associated with the abnormal endochondral ossification in AIS patients.

A review of pinealectomy-induced melatonin-deficient animal models for the study of etiopathogenesis of adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common orthopedic disorder of unknown etiology and pathogenesis. Melatonin and melatonin pathway dysfunction has been widely suspected to play an important role in the pathogenesis. Many different types of animal models have been developed to induce experimental scoliosis mimicking the pathoanatomical features of idiopathic scoliosis in human. The scoliosis deformity was believed to be induced by pinealectomy and mediated through the resulting melatonin-deficiency. However, the lack of upright mechanical spinal loading and inherent rotational instability of the curvature render the similarity of these models to the human counterparts questionable. Different concerns have been raised challenging the scientific validity and limitations of each model. The objectives of this review follow the logical need to re-examine and compare the relevance and appropriateness of each of the animal models that have been used for studying the etiopathogenesis of adolescent idiopathic scoliosis in human in the past 15 to 20 years.

Effect of eccentric isokinetic exercise on muscle strength and functional recovery after anterior cruciate ligament reconstruction.

Background: Previous studies have shown isokinetic exercise forms an important part in reconditioning the patients after anterior cruciate ligament reconstruction (ACLR) in regaining muscle strength and knee function. Although eccentric isokinetic training has been shown to enhance quadriceps muscle strength, the application toward benefiting patients after ACLR remains controversial. The present study aims to investigate the benefits of eccentric over concentric isokinetic exercises on knee muscle strength and its value in later stage of rehabilitation, including the return-to-sport. Methods: Thirty-six patients who had undergone ACLR for 4-to-6 months were assigned to receive either eccentric or concentric isokinetic training weekly for six weeks on top of their standardized post-operative exercise programme. The assessments include isokinetic test on the peak torques of quadriceps and hamstrings, single-leg hop test and ability to return-to-sport. Results: Both groups demonstrated significant gains on peak torques in quadriceps and hamstrings after training. At post-intervention, the peak torques for both quadriceps (p = 0.005) and hamstrings (p = 0.017) of the ACL-reconstructed limb from eccentric training were significantly higher than concentric training. The significant improvement was similarly demonstrated in the limb symmetry index (LSI) in hamstrings (p = 0.016) of the ACL-reconstructed limb from eccentric training. Moreover, eccentric group performed significantly better in single-leg hop tests (p = 0.042). Most importantly, eccentric group have higher percentages of return-to-sport (55.6 %) than concentric group (27.8 %). Conclusion: A 6-week course of eccentric isokinetic training was more effective than concentric isokinetic training in increasing quadriceps and hamstrings strength in terms of peak torques. Importantly, the better functional performance after the eccentric isokinetic exercise account for higher return-to-sport ratio.

Antiviral Effects and Mechanisms of Green Tea Catechins on Influenza: A Perception on Combating Symptoms from COVID-19.

Over the centuries, influenza and its associated epidemics have been a serious public health problem. Although vaccination and medications (such as neuraminidase inhibitors) are the mainstay of pharmacological approaches to prevent and treat influenza, however, frequent mutations in the influenza genome often result in treatment failure and resistance to standard medications which limit their effectiveness. In recent years, green tea catechins have been evaluated as potential anti-influenza agents. Herein, in this review, we highlighted the effects and mechanisms underlying the inhibitory effects of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea, against different influenza viral infections, and their clinical benefits toward prevention and treatment. In addition, as the severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) causes the outbreak of COVID-19 pandemic, our review also delineates the current perspective on SARS-CoV-2 and future insights as to the potential application of EGCG on suppressing the flu-like symptoms caused by COVID-19.

Serum vitamin D insufficiency is correlated with quadriceps neuromuscular functions in patients with anterior cruciate ligament injury: A preliminary study.

Background: This study aimed to investigate the correlations of serum vitamin D insufficiency with quadriceps neuromuscular function in patients with anterior cruciate ligament (ACL) injury. Methods: A cross-sectional study was conducted. Eighteen patients with a primary, unilateral ACL injury who had insufficient serum vitamin D concentrations (<30 ng/ml) were recruited for the study. Bilateral quadriceps neuromuscular function, including maximal strength, the speed of rapid contraction, and inhibition, were measured on an isokinetic dynamometer with the hip and the knee joint flexion at 90° and 45°, respectively. Quadriceps strength was measured by maximal voluntary isometric contractions (MVIC); the speed of rapid contraction was quantified by the rate of torque development (RTD), which was divided into the early (RTD0-50) and the late phase (RTD100-200); quadriceps inhibition was quantified by the central activation ratio (CAR). Serum vitamin D concentration was quantitatively determined by serum 25(OH)D concentration measured by the 25(OH)D ELISA kit. The Spearman rank correlation analysis was used to examine the correlation between the vitamin D concentration and bilateral quadriceps MVIC, RTD0-50, RTD100-200, and CAR, respectively. Results: The results of Spearman rank correlation analyses showed that the serum 25(OH)D concentration was significantly correlated with bilateral quadriceps MVIC (injured: r = 0.574, p = 0.013; uninjured: r = 0.650, p = 0.003) and RTD0-50 (r = 0.651, p = 0.003), and CAR (r = 0.662, p = 0.003) on the uninjured limb. However, no significant correlations were found between the serum 25(OH)D concentration and the other outcomes. Conclusions: The serum vitamin D concentration correlates with quadriceps neuromuscular function in patients with ACL injury who had vitamin D insufficiency.

Vitamin D as an intervention for improving quadriceps muscle strength in patients after anterior cruciate ligament reconstruction: study protocol for a randomized double-blinded, placebo-controlled clinical trial.

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.

The predictors to self-reported and performance-based physical function in knee osteoarthritis patients: a cross-sectional study.

Background: Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors. Methods: 135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function. Results: BMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r 2 = -0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r 2 = -0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (ß = 0.712, p < 0.001), knee flexor muscle strength (ß = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: ß = -0.428, p < 0.001) and flexor muscle strength (6MGS: ß = 0.367, p < 0.001), were the main predictors with performance-based physical function. Conclusion: Pain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.