Lanatoside C inhibits herpes simplex virus 1 replication by regulating NRF2 distribution within cells.

BACKGROUND: In the past decades, extensive research has been conducted to identify new drug targets for the treatment of Herpes simplex virus type 1 (HSV-1) infections. However, the emergence of drug-resistant HSV-1 strains remains a major challenge. This necessitates the identification of new drugs with novel mechanisms of action. Lanatoside C (LanC), a cardiac glycoside (CG) approved by the US Food and Drug Administration (FDA), has demonstrated anticancer and antiviral properties. Nevertheless, its potential as an agent against HSV-1 infections and the underlying mechanism of action are currently unknown. PURPOSE: This study aimed to investigate the antiviral activity of LanC against HSV-1 and elucidate its molecular mechanisms. METHODS: The in vitro antiviral activity of LanC was assessed by examining the levels of viral genes, proteins, and virus titers in HSV-1-infected ARPE-19 and Vero cells. Immunofluorescence (IF) analysis was performed to determine the intracellular distribution of NRF2. Additionally, an in vivo mouse model of HSV-1 infection was developed to evaluate the antiviral activity of LanC, using indicators such as intraepidermal nerve fibers (IENFs) loss and viral gene inhibition. RESULTS: Our findings demonstrate that LanC significantly inhibits HSV-1 replication both in vitro and in vivo. The antiviral effect of LanC is mediated by the perinuclear translocation of NRF2. CONCLUSIONS: LanC exhibits anti-HSV-1 effects in viral infections, which are associated with the intracellular translocation of NRF2. These findings suggest that LanC has the potential to serve as a novel NRF2 modulator in the treatment of viral diseases.

Treatment Efficacy and Technical Advantages of Temporary Spinal Nerve Root Stimulation Compared to Traditional Spinal Cord Stimulation for Postherpetic Neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is a common complication after herpes zoster infection. While conventional dorsal column temporary spinal cord stimulation (tSCS) has been shown as an effective treatment option for this pain condition, recent data suggests ipsilateral temporary spinal nerve root stimulation (tSNRS) as a safe alternative for treating PHN. However, there is no direct clinical comparison between the newer tSNRS and the traditional tSCS. OBJECTIVES: The current retrospective study aimed to describe the technical factors and the therapeutic efficacy of tSNR for patients with unilateral PHN and to compare these parameters with those treated with tSCS. STUDY DESIGN: Retrospective cohort study. SETTING: Single-center study in a large academic hospital. METHODS: One hundred sixty patients with unilateral PHN who underwent 7-14 days of tSCS (n = 109) or tSNRS (n = 51) treatment were included. Technical factors between the 2 groups, such as procedure time, radiation dosage, number of electrodes used, number of stimulation parameter adjustments, and average cost, were compared. Treatment efficacy, measured by analgesic coverage, pain visual analog scale (VAS), total analgesic agent consumption, Pittsburgh sleep quality index (PSQI), and physical and mental quality of life, were also compared between the 2 groups at baseline, post-procedure, and 3 months after stimulation treatment. RESULTS: Patients who underwent tSNRS reported significant improvement in pain level, sleep quality, and overall quality of life immediately postprocedure and during the follow-up period. This therapeutic effect was comparable to the tSCS group. Moreover, tSNRS achieved this therapeutic effect with a fewer number of implanted electrodes and stimulation adjustments than tSCS. The precision and consistency of the tSNRS technique were associated with a significant overall lower cost, a shorter procedure time, and less intraoperative radiation exposure in the tSNRS group than in those who received tSCS. LIMITATIONS: The current retrospective cohort study was limited by its relatively short follow-up period. Also, the selection of stimulation techniques was not randomized. CONCLUSIONS: While tSNRS provides similar therapeutic efficacy compared to tSCS for patients with unilateral PHN; it offers several technical advantages. These advantages include shorter procedure time, less radiation exposure, fewer implanted electrodes, more effective stimulation, and lower overall cost.

The Modified WHO Analgesic Ladder: Is It Appropriate for Chronic Non-Cancer Pain?

INTRODUCTION: From 1986, the World Health Organization (WHO) analgesic ladder has been used as the simple and valuable pain-relieving guidance in the pharmaceutical pain management, however, with the development of medical history, notions about pain physiology and pain management have already updated. Is the analgesic ladder still appropriate for chronic non-cancer pain (CNCP) patients? This study aims to analyse the current usage of the analgesic ladder in patients with CNCP by evaluating previously published pertinent studies. METHODS: Literature published in English from January 1980 to April 2019 and cited on PubMed database was included. Analysis on the analgesic ladder, current status of CNCP management, and a new revised ladder model were developed based on relevant literature. RESULTS: The WHO analgesic ladder for cancer pain is not appropriate for current CNCP management. It is revised into a four-step ladder: the integrative therapies being adopted at each step for reducing or even stopping the use of opioid analgesics; interventional therapies being considered as step 3 before upgrading to strong opioids if non-opioids and weak opioids failed in CNCP management. DISCUSSION: A simple and valuable guideline in past years, the WHO analgesic ladder is inappropriate for the current use of CNCP control. A revised four-step analgesic ladder aligned with integrative medicine principles and minimally invasive interventions is recommended for control of CNCP.

Tai Chi for patients with mild cognitive impairment: A protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Mild cognitive impairment (MCI) is an intermediate stage between the cognitive changes of normal aging and early dementia. Tai Chi (TC) may be particularly beneficial to patients with MCI due to its whole-body coordination characteristics. This systematic review protocol aims to outline the methods that will be used to assess the comparative effectiveness and safety of TC for MCI through a systematic review and meta-analysis. METHODS: A systematic review will identify and evaluate randomized controlled trials (RCTs) that examined the effects and safety of TC compared to a placebo, conventional treatment, and no treatment on cognitive function in individuals with MCI. Studies from databases of MEDLINE, PubMed, Embase, Global Health, Cochrane Library, and Scopus from January 1990 to March 2019 reported in English will be searched. Two independent reviewers will screen the studies for inclusion with the eligibility criteria and extract data. Risk of bias of individual studies will be assessed in line with Cochrane risk of bias tool. The overall quality of cumulative evidence will be assessed using selected Grading of Recommendations, Assessment, Development, and Evaluations criteria. Statistics will be used for heterogeneity assessment, sensitivity analysis, data synthesis, generating funnel plots, and subgroup analysis. Meta-analysis will be performed, if sufficiently homogeneous studies are found. A narrative synthesis will be conducted, grouping studies by exposure and outcome definitions, and describing any differences by subgroups. RESULTS: This study will provide practical and targeted evidence in investigating the impact of TC exercise for individuals with MCI. CONCLUSION: The findings of our study will provide updated evidence to determine whether TC is an effective intervention to patients with MCI. TRIAL REGISTRATION NUMBER: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42019125104.

Combining Botulinum Toxin (A) Injection With Peripheral Nerve Stimulation in a Patient for Intractable Ophthalmic Postherpetic Neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is a particularly challenging neuropathic pain condition, especially when it involves the trigeminal nerve. Peripheral nerve stimulation (PNS) can provide 50-70% improvement in pain to many who fail medical management. However, this pain relief can be incomplete, and residual pain may persist for many years. Here we report a case that was successfully managed by a novel technique of combining supraorbital nerve stimulation with botulinum toxin type A (BTA) for intractable ophthalmic PHN. CASE: A 73-year-old man presented with burning, stabbing, constant, severe pain in the ophthalmic branch of left trigeminal nerve dermatome, which had been present for a year. A permanent PNS provided 50% pain relief, but there was residual pain in the left orbital area that has remained, which was refractory to pharmaceutical treatment. Because of the restricted location of the residual pain, this patient was an appropriate candidate for BTA injection. RESULTS: Following the BTA injection, the patient had a significant improvement in pain relief and this continued for six months without any oral medication. CONCLUSIONS: In a patient with trigeminal PHN, local injection of BTA effectively reduced pain remaining after treatment with PNS.