Comparison of the Efficacy of an Anchored Cage with Unidirectional and Bidirectional Screw Fixation in Single-Level Cervical Discectomy and Fusion Surgery.

AIM: To compare, and to analyze the clinical and radiological signs between bidirectional and unidirectional screw fixation in single level cervical discectomy and fusion surgery. MATERIAL AND METHODS: We retrospectively reviewed the data collected from 90 patients and divided them into the upper or lower spine fixation group (unidirectional) and the normal upper and lower spine fixation group (bidirectional). The patients' demographic data and preoperative and postoperative (24 months) clinical outcomes were collected. Pre- and postoperative (immediately and at 3, 6, 12, and 24 months) changes in the segmental angle in the operating field (SA), cervical lordosis, C2-7 sagittal vertical axis, and active disc height (aDH) were evaluated. We also compared the rate of fusion and muscle size change between the groups. RESULTS: The operation time in the bidirectional screw fixation group was significantly longer than that in the unidirectional screw fixation group ( > 6 min; p=0.03). There was no significant difference between the two groups in radiographic parameters before and immediately after surgery. From 3 months postoperatively, the unidirectional group had significantly higher SA and aDH than the bidirectional group (p=0.03). The fusion rate was higher in the bidirectional screw fixation group than in the unidirectional group, but this was not statistically significant (97% vs. 88%, p=0.07). CONCLUSION: The results of this study suggest that unidirectional screw fixation surgery can be useful as it has been associated with simple surgery, short surgery time, and maintenance of the lordotic curvature of SA and disc height.

Efficacy of Poria Cocos Extract on Sleep Quality Enhancement: A Clinical Perspective with Implications for Functional Foods.

BACKGROUND: Since the outbreak of the pandemic started, an increase in the number of sleep disorders, including insomnia and poor sleep quality, has been seen. The pattern will probably continue. METHODS: This study focuses on the preparation and clinical testing of Poria cocos extract in treating suboptimal sleep quality. The optimal extraction method utilized a 75% ethanol concentration, and the clinical investigation involved subjects with defined poor sleep taking 800 mg of the extract nightly, assessed using the Sleep Questionnaire and polysomnography. The non-parametric Wilcoxon signed-rank test was used for statistical analysis due to the non-normal distribution of the collected data. RESULTS: The study involved 21 insomnia sufferers with a mean age of 55 who were administered Poria cocos extracts. The findings of the study indicate a statistically significant rise in the overall duration of sleep (from 327.395 ± 43.2 min to 356.516 ± 63.21 min, p = 0.014). Additionally, there was a notable decrease in the level of arousal during sleep (from 76.316 ± 44.78 min to 47.989 ± 42.38 min, p = 0.009), and an improvement in the sleep severity index of the sleep questionnaire test. CONCLUSIONS: Poria cocos as a natural substance could improve quality of sleep, based on the findings. The study investigates Pachymic acid, a substance found in Poria cocos, as a potential indicator for the development of sleeping aids.

The Positive Effects of Poria cocos Extract on Quality of Sleep in Insomnia Rat Models.

Sleep disorders may have various causes and can incur mental and/or physical symptoms, and affect an individual's quality of life. In this study, we confirm that the Poria cocos extract (PCET) can improve sleep quality and structure by promoting inhibitory neurotransmission via the γ-aminobutyric acid (GABA) type A (GABAA) receptors based on the mechanisms revealed in the experiment with superior cervical ganglion neurons. Pentobarbital-induced sleep tests were conducted in order to determine whether the PCET extract improves the sleep quality and structure in normal ICR mice. Sleep latency and duration were checked with the righting reflex. To simulate the state of awakening as well as a normal sleep state, caffeine was administered orally before the PCET diet. After oral gavage of PCET, sleep latency was decreased, and total sleep duration was increased in normal and caffeine-induced sleep disturbance state. In the ACTH-induced sleep disturbed models, administration of PCET significantly reduced the sleep latency and increased the non-REM sleep duration, which was analyzed in real-time EEG by implanting wireless electrodes in SD rats. PCET was found to improve the sleep quality under a normal sleep state through the GABAA receptor; it also promoted and improved the sleep quality and sleep structure in both the arousal activation state and stress-based sleep disturbance.

Change in the Alignment and Distal Junctional Kyphosis Development after Posterior Cervical Spinal Fusion Surgery for Cervical Spondylotic Myelopathy - Risk Factor Analysis.

OBJECTIVE: This study analyzed the risk factors in patients who developed distal junctional kyphosis (DJK) after posterior cervical fusion. METHODS: We retrospectively analyzed the clinical and radiographic outcomes of 64 patients, aged ≥18 years (51 and 13 male and female patients, respectively), who underwent single-staged multilevel (3-6 levels) posterior cervical fusion surgery due to multiple cervical spondylotic myelopathy. The surgeries were performed by a single spinal surgeon between January 2012 and December 2017. Demographic data, clinical outcomes, and radiological results were collected. We divided the patients into a DJK group and a non-DJK group according to the presence of DJK and investigated the risk factors by comparing the differences between the two groups. RESULTS: Of the 64 patients, 13 developed DJK. No significant differences in clinical results were observed between the two groups before and immediately after the surgery. At the final follow-up, a higher visual analog score for neck pain was observed in the DJK group compared to the non-DJK group (p<0.01). The DJK group had a significantly lower T1 slope and a significantly higher C2-7 sagittal vertical axis (SVA) before surgery compared to the non-DJK group (p=0.03 and p<0.01, respectively). Immediately after surgery, the difference between the two groups decreased and no significant difference was observed. However, at the last followup, a significantly higher C2-7 SVA was observed in the DJK group (p<0.01). At the last follow up, there is no discrepancy in T1S-CL. In multiple logistic regression analysis, preoperative higher C2-7 SVA and preoperative lower T1 slope were identified as independent risk factors (p=0.03 and p<0.01, respectively). As a result, it was confirmed that DJK occurred along the process of returning to preoperative values. CONCLUSION: DJK can be considered to be caused by cervical misalignment due to excessive change in the surgical site in patients with low T1 slope and high C2-7 SVA before surgery. This also affects the clinical outcome after surgery. It is recommended to refrain from excessive segmental lordosis changes during multilevel cervical post fusion surgery, especially in patients with a small preoperative T1 slope and a large SVA value.

A retrospective controlled study of postoperative fever after posterior lumbar interbody fusion due to degenerative lumbar disease.

BACKGROUND: Postoperative fever is a common feature of spinal surgery. When fever occurs postoperatively in patients, surgeons are eager to rule out an infection. There are many reports about postoperative fever and infection; however, only a few have described the relationship between degenerative spinal disease and postoperative fever. This study aimed to investigate the causes of postoperative fever in patients with degenerative lumbar disease undergoing posterior screw fixation and interbody fusion and compare patients with non-pathologic fever and infected febrile patients. METHODS: From March 2015 to February 2016, 263 patients with degenerative lumbar disease underwent posterior lumbar screw fixation and interbody fusion surgery in our institution. We performed risk factor analysis by categorizing patients as afebrile and febrile. Comparisons were made between afebrile patients and patients with non-pathologic fever, and an analysis was performed between patients with non-pathologic fever and patients with febrile infection. We compared each group by examining the demographic factors before surgery, surgery features, drain duration, and postoperative transfusion. The postoperative day (POD) of fever onset, postoperative fever duration, and blood sample results in patients with fever were investigated. RESULTS: The drain duration was found to be an important factor between the afebrile febrile groups and between the non-pathologic fever and afebrile groups. POD of fever occurred earlier in the non-pathologic group than in the infection group (p = 0.04), and the duration of fever was shorter in the non-pathologic fever group than in the infection group (p = 0.01). Higher procalcitonin levels were observed at POD 5 in the infection group than in the non-pathologic fever group. (p < 0.01) The accidental dural rupture rate was higher in the infected group (p = 0.02); this was thought to be caused by the long non-ambulatory period after surgery. CONCLUSION: This study identified risk factors and differences between infectious diseases associated with postoperative fever. A significant risk factor for postoperative non-pathological fever was a shorter catheter drainage period. Fever after 3 days, fever for more than 4 days and higher procalcitonin levels after surgery suggest infection.

Exosome-Mediated Ultra-Effective Direct Conversion of Human Fibroblasts into Neural Progenitor-like Cells.

Exosomes, naturally secreted nanoparticles, have been introduced as vehicles for horizontal transfer of genetic material. We induced autologous exosomes containing a cocktail of reprogramming factors ("reprosomes") to convert fibroblasts into neural progenitor cells (NPCs). The fibroblasts were treated with ultrasound and subsequently cultured in neural stem cell medium for 1 day to induce the release of reprosomes composed of reprogramming factors associated with chromatin remodeling and neural lineage-specific factors. After being treated with reprosomes, fibroblasts were converted into NPCs (rNPCs) with great efficiency via activation of chromatin remodeling, so quickly that only 5 days were required for the formation of 1500 spheroids showing an NPC-like phenotype. The rNPCs maintained self-renewal and proliferative properties for several weeks and successfully differentiated into neurons, astrocytes, and oligodendrocytes in vitro and in vivo. Reprosome-mediated cellular reprogramming is simple, safe, and efficient to produce autologous stem cells for clinical application.

A novel antihypertension agent, sargachromenol D from marine brown algae, Sargassum siliquastrum, exerts dual action as an L-type Ca2+ channel blocker and endothelin A/B2 receptor antagonist.

We isolated the novel vasoactive marine natural products, (5E,10E)-14-hydroxy-2,6,10-trimethylpentadeca-5,10-dien-4-one (4) and sargachromenol D (5), from Sargassum siliquastrum collected from the coast of the East Sea in South Korea by using activity-guided HPLC purification. The compounds effectively dilated depolarization (50mMK+)-induced basilar artery contraction with EC50 values of 3.52±0.42 and 1.62±0.63µM, respectively, but only sargachromenol D (5) showed a vasodilatory effect on endothelin-1 (ET-1)-induced basilar artery contraction (EC50=9.8±0.6µM). These results indicated that sargachromenol D (5) could act as a dual antagonist of l-type Ca2+ channel and endothelin A/B2 receptors. Moreover, sargachromenol D (5) lowered blood pressure in spontaneous hypertensive rats (SHRs) 2h after oral treatment at a dose of 80mg/kg dose and the effect was maintained for 24h. Based on our ex vivo and in vivo experiments, we propose that sargachromenol D (5) is a strong candidate for the treatment of hypertension that is not controlled by conventional drugs, in particular, severe-, type II diabetes-, salt-sensitive, and metabolic disease-induced hypertension.

Anti-obesity potential of enzymatic fragments of hyaluronan on high-fat diet-induced obesity in C57BL/6 mice.

Hyaluronan has diverse biological activities depending on its molecular size. The hyaluronan fragments (50 kDa) can decrease adipogenic differentiation in vitro. However, in vivo anti-obesitic effects of hyaluronan fragments have not been elucidated. Therefore, we examined the anti-obesity effects of hyaluronan fragments on high-fat diet induced obesity in C57BL/6 mice. Oral administration of hyaluronan fragments (200 mg/kg for 8 weeks) decreased body weight, adipose tissues, serum lipid (low-density lipoprotein cholesterol, triglyceride), and leptin level. Hyaluronan fragments decreased the hypertrophy of adipose tissue and ameliorated liver steatosis. The mRNA expression of leptin was reduced in adipocyte by treatment with hyaluronan fragments. Additionally, hyaluronan fragments enhanced the mRNA expression of PPAR-α and its target genes UCP-2 and decreased mRNA expression of PPAR- γ and fatty acid synthase in liver. In conclusions, hyaluronan fragments had marked effects on inhibiting the development of obesity in obese mice fed the high-fat diet. It suggested that enhancing PPAR-α and suppressing PPAR-γ expression are two possible mechanisms for the anti-obesitic effect of hyaluronan fragments.

Enzymatic fragments of hyaluronan inhibit adipocyte differentiation in 3T3-L1 pre-adipocytes.

Hyaluronan has diverse biological activities depending on its molecular size. High molecular weight hyaluronan (2000 kDa) is a major component of extracellular matrix, and has been used in wounding healing, extracellular matrix regeneration, and in the treatment of osteoarthritis. Hyaluronan fragments can stimulate inflammation or induce loss of extracellular matrix. Hyaluronan is expressed during adipocyte differentiation, and down regulation of hyaluronan synthesis can reduce adipogenic differentiation. However, the direct effects of hyaluronan fragments on adipocyte differentiation have not been elucidated. Therefore, we prepared hyaluronan fragments by enzymatic digestion, and examined the inhibitory effects of these hyaluronan fragments on the accumulation of lipid droplets and on adipogenic gene mRNA expression in differentiating 3T3-L1 pre-adipocytes. Medium sized hyaluronan fragments (50 kDa) decreased lipid droplet accumulation in a dose-dependent manner. However, high molecular weight hyaluronan did not inhibit lipid droplet accumulation when used at a concentration of 600 µg/ml. Two or 4 day treatments with medium molecular weight of hyaluronan resulted in similar inhibitory levels of lipid accumulation as did treatment for 8 days. Medium sized hyaluronan inhibited the differentiation of 3T3-L1 pre-adipocytes during the early stages of adipogenesis. When 3T3-L1 cells were treated with 180 µg/ml of medium sized hyaluronan, the mRNAs for the master adipogenic transcription factors PPAR-γ and C/EBP-α were inhibited. Additionally, medium molecular weight hyaluronan suppressed mRNA expression of PPAR-γ target genes, including aP2 and FAS. This study is the first to report that medium molecular weight hyaluronan fragments can inhibit adipocyte differentiation.

Synthesis of alkylsulfonyl and substituted benzenesulfonyl curcumin mimics as dual antagonist of L-type Ca(2+) channel and endothelin A/B2 receptor.

We synthesized a library of curcumin mimics with diverse alkylsulfonyl and substituted benzenesulfonyl modifications through a simple addition reaction of important intermediate, 1-(3-Amino-phenyl)-3-(4-hydroxy-3-methoxy-phenyl)-propenone (10), with various sulfonyl chloride reactants and then tested their vasodilatation effect on depolarization (50 mM K(+))- and endothelin-1 (ET-1)-induced basilar artery contraction. Generally, curcumin mimics with aromatic sulfonyl groups showed stronger vasodilation effect than alkyl sulfonylated curcumin mimics. Among the tested compounds, six curcumin mimics (11g, 11h, 11i, 11j, 11l, and 11s) in a depolarization-induced vasoconstriction and seven compounds (11g, 11h, 11i, 11j, 11l, 11p, and 11s) in an ET-1-induced vasoconstriction showed strong vasodilation effect. Based on their biological properties, synthetic curcumin mimics can act as dual antagonist scaffold of L-type Ca(2+) channel and endothelin A/B2 receptor in vascular smooth muscle cells. In particular, compounds 11g and 11s are promising novel drug candidates to treat hypertension related to the overexpression of L-type Ca(2+) channels and ET peptides/receptors-mediated cardiovascular diseases.

Synthesis of diethylamino-curcumin mimics with substituted triazolyl groups and their sensitization effect of TRAIL against brain cancer cells.

A newly designed curcumin mimic library (11a-11k) with 2-ethylamino groups in a chalcone structure and variously substituted triazole groups as side chains was synthesized using the Huisgen 1,3-cycloaddition reaction between various alkynes (a-k) and an intermediate (10), with CuSO4 and sodium ascorbate in a solution mixture of chloroform, ethanol, and water (5:3:1) at room temperature for 5h. In the lactate dehydrogenase (LDH) release assay involving co-treatment with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and/or synthetic curcumin derivatives using TRAIL-resistant human CRT-MG astroglioma cells, the novel curcumin mimic library was found to effectively stimulate the cytotoxicity of TRAIL, causing mild cytotoxicity when administered alone. In particular, 11a and 11j are promising candidates for TRAIL-sensitizers with potential use in combination chemotherapy for brain tumors.

5E- and 5Z-farnesylacetones from Sargassum siliquastrum as novel selective L-type calcium channel blockers.

A specific blocker of L-type Ca(2+) channels may be useful in decreasing arterial tone by reducing the open-state probability of L-type Ca(2+) channels. The aim of the present study was to evaluate the farnesylacetones, which are major active constituents of Sargassum siliquastrum, regarding their vasodilatation efficacies, selectivities toward L-type Ca(2+) channels, and in vivo antihypertensive activities. The application of 5E-(farnesylacetone 311) or 5Z-farnesylacetone (farnesylacetone 312) induced concentration-dependent vasodilatation effects on the basilar artery that was pre-contracted with depolarization and showed an ignorable potential role of endothelial-derived nitric oxide. We also tested farnesylacetone 311 or 312 to determine their pharmacological profiles for the blockade of native L-type Ca(2+) channels in basilar arterial smooth muscle cells (BASMCs) and ventricular myocytes (VMCs), cloned L- (α1C/ß2a/α2δ), N- (α1B/ß1b/α2δ), and T-type Ca(2+) channels (α1G, α1H, and α1I). Farnesylacetone 311 or 312 showed greater selectivity toward the L-type Ca(2+) channels among the tested voltage-gated Ca(2+) channels. The ranked order of the potency for farnesylacetone 311 was cloned α1C≒L-type (BASMC)≒L-type (VMCs)>α1B>α1H>α1I>α1G and that for farnesylacetone 312 was cloned α1C≒L-type (BASMCs)≒L-type (VMCs)>α1H>α1G>α1B>α1I. The oral administration of the farnesylacetone 311 (80mg/kg) conferred potent, long-lasting antihypertensive activity in spontaneous hypertensive rats, but it did not alter the heart rate.

Mechanisms of motility change on trinitrobenzenesulfonic Acid-induced colonic inflammation in mice.

Ulcerative colitis is an inflammatory bowel disease (IBD) characterized by recurrent episodes of colonic inflammation and tissue degeneration in human or animal models. The contractile force generated by the smooth muscle is significantly attenuated, resulting in altered motility leading to diarrhea or constipation in IBD. The aim of this study is to clarify the altered contractility of circular and longitudinal smooth muscle layers in proximal colon of trinitrobenzen sulfonic acid (TNBS)-induced colitis mouse. Colitis was induced by direct injection of TNBS (120 mg/kg, 50% ethanol) in proximal colon of ICR mouse using a 30 G needle anesthetized with ketamin (50 mg/kg), whereas animals in the control group were injected of 50% ethanol alone. In TNBS-induced colitis, the wall of the proximal colon is diffusely thickened with loss of haustration, and showed mucosal and mucular edema with inflammatory infiltration. The colonic inflammation is significantly induced the reduction of colonic contractile activity including spontaneous contractile activity, depolarization-induced contractility, and muscarinic acetylcholine receptor-mediated contractile response in circular muscle layer compared to the longitudinal muscle layer. The inward rectification of currents, especially, important to Ca(2+) and Na(+) influx-induced depolarization and contraction, was markedly reduced in the TNBS-induced colitis compared to the control. The muscarinic acetylcholine-mediated contractile responses were significantly attenuated in the circular and longitudinal smooth muscle strips induced by the reduction of membrane expression of canonical transient receptor potential (TRPC) channel isoforms from the proximal colon of the TNBS-induced colitis mouse than the control.

Phenotype-specific down-regulation of nicotinic acetylcholine receptors in the pelvic ganglia of castrated rats: implications for neurogenic erectile dysfunction.

Pelvic ganglia (PG) play critical roles in relaying sympathetic and parasympathetic information from the spinal cord to the penile vasculature and, controlling the penile reflex. Animal studies have shown that androgen deprivation by castration causes erectile dysfunction (ED). Until now, however, neural mechanisms underlying castration-induced ED remain unclear. Therefore, we examined whether androgen deprivation down-regulates nicotinic acetylcholine receptors (nAchRs), which mediate fast excitatory synaptic transmission in the PG. Toward this end, neurogenic ED was demonstrated by measuring the intracavernous pressure in castrated rats. Real-time PCR analysis revealed that the transcripts encoding nAchR α3/α5/ß4 subunits were significantly down-regulated in the PG neurons. In addition, down-regulation of the nAchR subunits was reversed by replacement of testosterone. Patch-clamp experiments showed that the nAchR currents were selectively attenuated in the parasympathetic PG neurons innervating the penile vasculature, activation of which elicits penile erection. Taken together, our data suggest that phenotype-specific down-regulation of nAchRs in the PG neurons may contribute to the neurogenic ED in castrated rats.

Synthesis of two marine farnesylacetones that dilate the basilar arteries of rabbits.

We have synthesized novel vasodilatation farnesylacetones 1 and 2, which are major active constituents of Sargassum siliquastrum collected from the coast of the East Sea in Korea, in 9 steps. A test of the vasodilatation effect of synthetic intermediates and their deprotected compounds on the basilar arteries of rabbits revealed that 14 and 14-1 have a similar dilation effect as their target marine natural products 1 and 2.

Synthesis of sulfonyl curcumin mimics exerting a vasodilatation effect on the basilar artery of rabbits.

In order to discover novel small vasodilatory molecules for potential use in the treatment of vascular disease, we tested the vasodilatation effect of two types of synthetic curcumin mimics, amide type (3) and sulfonyl amide type (4), upon the basilar artery of rabbits. In general, the sulfonyl amide type mimic (4) is more potent than the amide type (3). Curcumin (1) and compounds 12 and 20 effectively dilated the basilar artery of white rabbits.

Vasodilatation effect of farnesylacetones, active constituents of Sargassum siliquastrum, on the basilar and carotid arteries of rabbits.

Two farnesylacetones, 311 and 312, major active constituents of Sargassum siliquastrum collected from the coast of the East Sea in Korea, showed a moderate vasodilatation effect on the basilar arteries of rabbits. Therefore, treatment with farnesylacetones 311 and 312 may selectively accelerate cerebral blood flow through dilatation of the basilar artery.

Selective vasodilatation effect of sargahydroquinoic acid, an active constituent of Sargassum micracanthum, on the basilar arteries of rabbits.

Sargahydroquinoic acid (2), a major active constituent of Sargassum micracanthum collected from the coast of the East Sea in Korea, showed a selective vasodilatation effect on the basilar arteries of rabbits. Therefore, treatment with sargahydroquinoic acid may selectively accelerate cerebral blood flow through dilatation of the basilar artery without lowering systemic blood pressure.

Nerve injury alters profile of receptor-mediated Ca2+ channel modulation in vagal afferent neurons of rat nodose ganglia.

Although nerve injury is known to up- and down-regulate some metabotropic receptors in vagal afferent neurons of the nodose ganglia (NG), the functional significance has not been elucidated. In the present study, thus, we examined whether nerve injury affected receptor-mediated Ca2+ channel modulation in the NG neurons. In this regard, unilateral vagotomy was performed using male Sprague-Dawley rats. One week after vagotomy, Ca2+ currents were recorded using the whole-cell variant of patch-clamp technique in enzymatically dissociated NG neurons. In sham controls, norepinephrine (NE)-induced Ca2+ current inhibition was negligible. Following vagotomy, however, the NE responses were dramatically increased. This phenomenon was in accordance with up-regulation of alpha2A/B-adrenergic receptor mRNAs as quantified using real-time RT-PCR analysis. In addition, neuropeptide Y (NPY) and prostaglandin E2 responses were moderately augmented in vagotomized NG neurons. The altered NPY response appears to be caused by up-regulation of Y2 receptors negatively coupled to Ca2+ channels. In contrast, nerve injury significantly suppressed opioid (tested with DAMGO)-induced Ca2+ current inhibition with down-regulation of micro-receptors. Taken together, these results demonstrated for the first time that the profile of neurotransmitter-induced Ca2+ channel modulation is significantly altered in the NG neurons under pathophysiological state of nerve injury.

Divalent metals differentially block cloned T-type calcium channels.

We tested divalent metals including Cu2+, Pb2+, and Zn2+ to determine their pharmacological profiles for blockade of cloned T-type Ca2+ channels (alpha1G, alpha1 H, and alpha1I). Effects of the metals were also evaluated for native low and high voltage-activated Ca2+ channels in rat sympathetic pelvic neurons. Cu2+ and Zn2+ blocked three T-type channel isoforms in a concentration-dependent manner with a higher affinity for alpha1H currents (IC50 = 0.9 microM and 2.3 microM). In pelvic neurons, only Zn2+ showed strong selectivity for T-type Ca2+ currents over high voltage-activated Ca2+ currents. Conversely, Pb2+ block on Ca2+ channels did not show distinctive selectivity. Taken together, these results suggest that besides Ni2+, Cu2+ and Zn2+ can be used as selective blockers of alpha1 H at low concentrations.