Andrographolide anti-proliferation and metastasis of hepatocellular carcinoma through LncRNA MIR22HG regulation.

Hepatocellular carcinoma (HCC) treatment is a major challenge. Although andrographolide (Andro) has an anti-proliferation effect on HCC, its underlying mechanism is not yet elucidated, and whether Andro can inhibit HCC metastasis has not been reported. The present study aimed to clarify whether Andro inhibits SK-Hep-1 cell proliferation and HCC metastasis, and the mechanisms. The results showed that Andro significantly reduced the survival of HCC cells and tumor weight and volume in tumor-bearing nude mice. Andro also triggered apoptosis of HCC cells and upregulated MIR22HG, Cleaved Caspase 9/7/3 expression levels, and downregulated BCL-2 mRNA, BCL-2 expression levels. Knockdown of MIR22HG or overexpression of HuR attenuated the effects of Andro on the signal transduction of mitochondrial apoptotic pathway and proliferation ability in HCC cells. Moreover, Andro significantly reduced the invasive ability of the cells and the level of HCC cell lung metastasis, upregulated miR-22-3p expression level and downregulated HMGB1 and MMP-9 expression levels. MIR22HG or miR-22-3p knockdown attenuated the effects of Andro on the signaling of HMGB1/MMP-9 pathway and invasive ability in HCC cells, while the overexpression of HMGB1 attenuated the inhibitory effects of Andro on the MMP-9 expression level and invasive ability in HCC cells. Thus, the regulation of MIR22HG-HuR/BCL-2 and MIR22HG/HMGB1 signaling pathways is involved in the anti-HCC proliferation and metastasis effects of Andro. This study provided a new pharmacological basis for Andro in HCC treatment and, for the first time, identified a natural product molecule capable of positively regulating MIR22HG, which has a robust biological function.

Authentication of Platycladus Orientalis Leaves and Its Five Adulterants by Combination of Morphology and Microscopic Characteristics, TLC, and HPLC Analysis.

BACKGROUND: Platycladus orientalis leaves (POL), as the source of the traditional Chinese medicine (TCM) Platycladi Cacumen, has frequently been found to be misused with five adulterants including Chamaecyparis obtusa leaves (COL), Cupressus funebris leaves (CFL), Juniperus virginiana leaves (JVL), Sabina chinensis leaves (SCL), and Juniperus formosana leaves (JFL). OBJECTIVE: The purpose of this study was to distinguish POL (fresh leaves) from its five adulterants (fresh leaves). METHODS: The micromorphological features in terms of transection and microscopic characteristics of POL and adulterants were captured and compared using the an microscope. Both HPLC and TLC methods for the simultaneous determination of six bioactive flavonoids (myricitrin, isoquercitrin, quercitrin, amentoflavone, afzelin, and hinokiflavone) have been developed. RESULTS: There were significant differences in microscopic features of transverse section and powders. The TLC results suggested that the spots of myricitrin in POL were more obvious than those in the five adulterants. The contents of myricitrin and quercitrin, or the total content of flavonoids in POL, determined by HPLC, were significantly higher than those in the adulterants. CONCLUSION: POL was successfully distinguished from its five adulterants by the comparison of morphology, microscopic characteristics, and chemical profiles. HIGHLIGHTS: This research provides a comprehensive morphology, microscopic identification, TLC, and HPLC analysis for authenticating POL and its five adulterants.

Additional value of auricular intradermal acupuncture alongside selective serotonin reuptake inhibitors: a single-blinded, randomized, sham-controlled preliminary clinical study.

BACKGROUND: To evaluate the antidepressant effects of auricular intradermal acupuncture (AIA) of areas innervated by both the auricular branch of the vagus nerve and the trigeminal nerve. METHODS: Forty-nine patients with depression were randomly allocated into an AIA group (n = 25) and a sham AIA group (n = 24). Both groups received selective serotonin reuptake inhibitors (SSRIs) as conventional treatment. The AIA group received AIA stimulation, and the sham AIA group received sham AIA, which constituted being subjected to an attached needle that did not penetrate the skin. The needles were retained for 4 h each session, with five sessions a week for a total duration of 2 weeks. The outcomes were assessed by the 17-item Hamilton depression rating scale (HAMD-17), five factors (sleep disorder, retardation, cognitive dysfunction, anxiety/somatization, and weight) and self-rating depression scale (SDS) at weeks 0, 1, and 2. RESULTS: Fifty-four patients were randomly assigned to the AIA (n = 27) and sham AIA group (n = 27), of whom 25 patients in the AIA and 24 patients in the sham AIA group were analyzed. AIA-treated patients displayed a significantly greater reduction from baseline in HAMD-17 scores (p = 0.03) and SDS scores (p = 0.02) at week 2 compared to patients receiving sham AIA. The AIA intervention also produced a higher rate of clinically significant responses in sleep disorders (p = 0.07) compared to sham AIA. No adverse events occurred in either group. CONCLUSION: According to the findings of this preliminary study, AIA appears to have additional value compared to SSRIs alone in treating patients with depressive disorder.

Evoking the Withdrawal Reflex via Successive Needle-Pricking on the Plantar and Dorsal Aspect of the Foot Increases the FMA of the Lower Limb for Poststroke Patients in Brunnstrom Stage III: A Preliminary Study.

The withdrawal reflex is a defensive reaction to nociceptive stimuli and can be used to regulate locomotor gait during rehabilitation. We investigated the effect of successive needle-pricking of the plantar and dorsal foot surfaces on poststroke lower limb function. Thirty-five hemiplegic patients, within one month after primary stroke, with an affected lower limb (Brunnstrom stage III) were randomly divided into intervention and control groups. Both groups received routine drug treatment, rehabilitation training, and upper limb acupuncture treatment on the hemiplegic side. The control group also received routine acupuncture on the hemiplegic side of the lower limb, while the intervention group received successive needle-pricking on the sole and instep of both the unaffected and affected side feet. Outcomes were assessed before inception (D0) and after three (D3) and six (D6) treatment days, using Brunnstrom stage (Ueda assessment), total Fugl-Meyer lower extremity assessment (FMA-LE) and its subscores (FMA-LE-ss), active lower limb range of motion (AROM-LL), Modified Ashworth Scale Score (MAS-LL), and manual muscle testing (MMT-LL). The Brunnstrom stage was better in the intervention group than in the control group at both D3 and D6 (P < 0.01). The total FMA-LE score and sections B, C, D, and G FMA-LE-ss were significantly better in the intervention group than in the control group at D3 and D6 (P < 0.05). The AROM-LL hip and knee flexion and hip extension improved more in the intervention group than in the control group (P < 0.05). In the intervention group, MAS-LL hip flexion significantly improved at D6 (P < 0.01). Improvement in lower limb joints on the MMT-LL in the intervention group exceeded that in the control group at D6 (P < 0.01). Successive needle-pricking on the plantar and dorsal foot aspects of Brunnstrom stage III in poststroke patients contributed to rapid lower limb motor function improvement via the withdrawal reflex. This trial is registered with ChiCTR1900020633.

Auricular Intradermal Acupuncture as a Supplementary Motor Rehabilitation Strategy in Poststroke Patients: A Randomized Preliminary Clinical Study.

We have explored the potential of auricular intradermal acupuncture (AIA) in standard rehabilitation and acupuncture treatment for motor recovery in poststroke patients. This was a randomized, controlled preliminary clinical study in which the patients were randomly assigned to the CT group (conventional treatment, standard rehabilitation, and routine acupuncture) or AIA group (AIA combined with conventional treatment) and underwent 6 sessions in 1 week (6 days). Standard procedures and previously reported acupuncture points were used. Clinical outcomes were measured by the Fugl-Meyer motor assessment (FMA) of flexor and extensor synergy movement (FSM and ESM) of the upper and lower extremities (UE and LE) at days 0, 3, and 6. The assessment was performed by blinded assessors. The AIA group showed a significant increase in FMA-UE/FMA-LE scores on day 3 (P=0.012 and 0.001, respectively) and day 6 (P=0.041 and P < 0.001, respectively), but this was not observed in the CT group. Furthermore, unlike the CT group, the AIA group exhibited a significant increase in the FMA-LE score on day 3 (P=0.004) and the FMA-UE scores on day 6 (P=0.048). Finally, the correlation between ESM and FMA-UE/FMA-LE was higher than that between FSM and FMA-UE/FMA-LE after treatment: for ESM and UE, r = 0.759, P=0.007; for ESM and LE, r = 0.697, P=0.003; for FSM and UE, r = 0.604, P=0.049; for FSM and LE, r = 0.347, P=0.188. AIA is useful for motor rehabilitation in poststroke patients, particularly in terms of improving extensor synergy. This trial is registered with CHiCTR1800020150.

[Professor SHENG Can-ruo's academic thoughts and acupoint selection experience for hot flashes].

Professor SHENG Can-ruo is a well-known national veteran doctor with over 70 years of clinical experience. He has unique academic thoughts and clinical experience for common diseases and some difficult and complicated diseases. This paper mainly introduces professor SHENG 's syndrome-differentiation thought and experience of acupoint selection for hot flashes. It is emphasized that common hot flashes, such as hot flashes and night sweats, are different between yin and yang. While regulating yin and yang, more attention should be paid to ying-wei harmony, which is not only suitable for women's perimenopausal syndrome, but also for a series of clinical diseases caused by refractory drugs such as endocrine therapy after breast cancer surgery. At the same time of acupoint selection based on syndrome differentiation, a more rational prescriptions should be made according to the duration of the disease and the experience acupoints to improve the clinical efficacy.

Biological Activities of Phenolics from the Fruits of Phyllanthus emblica L. (Euphorbiaceae).

Seven phenolic compounds, 1 - 7, including a new organic acid gallate, mucic acid 1-ethyl 6-methyl ester 2-O-gallate (7), were isolated from the MeOH extract of the fruits of Phyllanthus emblica L. (Euphorbiaceae). The structures were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. Upon evaluated for their antioxidant abilities by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. The inhibitory activities against melanogenesis in B16 melanoma cells induced by α-MSH, as well as cytotoxic activities against four human cancer cell lines were also evaluated. All phenolic compounds, 1 - 7, exhibited potent antioxidant abilities (DPPH: IC50 5.6 - 12.9 µm; ABTS: 0.87 - 8.43 µm Trolox/µm; FRAP: 1.01 - 5.79 µm Fe2+ /µm, respectively). Besides, 5 - 7, also exhibited moderate inhibitory activities against melanogenesis (80.7 - 86.8% melanin content), even with no or low toxicity to the cells (93.5 - 101.6% cell viability) at a high concentration of 100 µm. Compounds 1 - 3 exhibited cytotoxic activity against one or more cell lines (IC50 13.9 - 68.4%), and compound 1 with high tumor selectivity for A549 (SI 3.2).

Anticonvulsant effect of unilateral anterior thalamic high frequency electrical stimulation on amygdala-kindled seizures in rat.

Deep brain stimulation (DBS) is an emerging treatment of epilepsy. Anterior nucleus of the thalamus (ANT) is considered to be an attractive target due to its close connection to the limbic structures and wide regions of neocortex. In this study, we examined the effect of unilateral high frequency stimulation (HFS) of the ANT on amygdala-kindled seizures in Wistar rats. When fully-kindled seizures were achieved by daily amygdala kindling, HFS (15 min train of 100 µs pulses at 200 Hz and 450-800 µA) was delivered to the ipsilateral or contralateral ANT immediately before the kindling stimulation for 15 days. HFS of the ipsilateral ANT significantly decreased the incidence of generalized seizures and the mean behavioral seizure stage and afterdischarge duration (ADD), and shortened cumulative ADD and cumulative generalized seizure duration. Furthermore, HFS of the ipsilateral ANT significantly increased the afterdischarge threshold (ADT). Our data suggest that unilateral HFS of the ANT may be an effective method of inhibiting kindled seizures by suppressing the susceptibility to seizures and generating long lasting anti-epileptic effect preventing the recurrence of kindled seizures, providing an alternative to bilateral ANT DBS for refractory epilepsy.