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Tibetan medicine Si-Wei-Qiang-Wei Powder ameliorates cholecystitis via inhibiting the production of pro-inflammatory cytokines and regulating the MAPK signaling pathway.

Si-Wei-Qiang-Wei Powder (SWQ) is a formulated traditional Tibetan medicine preparation that has been used clinically to treat liver and gallbladder diseases for centuries. Previous work has confirmed its clinical effectiveness, however, the specific mechanism of SWQ is still unknown.

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TRPV4 activation increases the expression of CD207 (Langerin) of monocyte-derived Langerhans cells, without affecting their maturation.

Langerhans cells (LCs) are the sole professional antigen-presenting cell normally found in the human epidermal compartment. Research into their physiological role is hindered by the fact that they are invariably activated during isolation from the skin. To overcome this challenge, we turned to a monocyte-derived LC model (moLC), which we characterized with RNASeq, and compared the transcriptome of moLCs to donor-matched immature dendritic cells. We found that moLCs express markers characteristic of LC2 cells, as well as transient receptor potential vanilloid 4 (TRPV4). TRPV4 is especially important in skin, as it has been linked to conservation of the skin barrier, immunological responses as well as acute and chronic itch, but we know little about its function on LCs. Our results show that TRPV4 activation increased the expression of Langerin and led to increased intracellular calcium concentration in moLCs. Regarding the functionality of moLCs, we found that TRPV4 agonism had a mitigating effect on their inflammatory responses, since it decreased their cytokine production, and T cell activating capability. As TRPV4 has emerged as a potential therapeutic target in dermatological conditions, it is important to highlight LCs as a novel target of these therapies.

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Usefulness of discography, discoblock and a new mechanical method for identifying a painful segment/disc.

We previously described a procedure for eliciting deep spatial discrimination of individual segments in the healthy lumbar spine of normal subjects: the percutaneous mechanical provocation (PMP) test. Our goal was to devise a method for accurate identification of the spinal level of pathology in chronic low-back pain (CLBP). In the present study, we validated the PMP test, using a subgroup of CLBP patients with isthmic spondylolisthesis (IS). Because there is clinical consensus that IS back pain originates in the slipped segment/disc, the level of pathology can be directly compared to the result of the PMP test. The test is agnostic with respect to the underlying pathological mechanism, and therefore might be useful in identifying the involved segment(s) irrespective of the painful structure.

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Nerve injury-induced upregulation of apolipoprotein E in dorsal root ganglion participates in neuropathic pain in male mice.

Apolipoprotein E (ApoE) is an apolipoprotein involved in lipid metabolism and is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS). The aim of this study is to explore the role of ApoE in the pathological development of neuropathic pain. First, we examined the location of ApoE in the dorsal root ganglion (DRG) and spinal cord in male mice using immunohistochemistry, and found that ApoE was predominantly expressed in DRG satellite glial cells (SGCs) and macrophages and spinal cord astrocytes. Using a spinal nerve ligation (SNL)-induced neuropathic pain mouse model, we found that nerve injury caused an increase in ApoE expression in the injured DRGs, but not in the spinal cord after SNL surgery. Furthermore, we observed reduced SNL-induced pain hypersensitivity in ApoE knockout mice compared to wild-type mice. Moreover, an antisense oligonucleotide (ASO) targeting the Apoe gene sequence, which was microinjected into the DRG or administered intrathecally, not only reduced ApoE expression in DRG but also attenuated SNL-induced pain hypersensitivity. Finally, we found that a tyrosine kinase receptor AXL, which was previously demonstrated to contribute to neuropathic pain, may mediate ApoE function under neuropathic pain condition. In conclusion, our data suggest that ApoE in DRG promote pain hypersensitivity via the DRG membrane receptor AXL in neurons under neuropathic pain conditions. This study revealed a novel mechanism between lipid homeostasis and neuropathic pain.

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How Does Changing the Time to Surgery Affect the Recurrence of Post-Traumatic Trigeminal Neuropathic Pain.

The recurrence of post-traumatic trigeminal neuropathic pain (PTTNp) following peripheral microneurosurgery continues to be poorly understood. The objective of this study was to determine if the time from injury to surgery of the trigeminal nerve in patients with PTTNp affected the recurrence of PTTNp following surgery.

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The role and mechanism of flavonoid herbal natural products in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine that presents clinically with abdominal pain, mucopurulent stools, and posterior urgency. The lesions of UC are mainly concentrated in the rectal and colonic mucosa and submucosa. For patients with mild to moderate UC, the best pharmacological treatment includes glucocorticoids, immunosuppressants, antibiotics, and biologics, but the long-term application can have serious toxic side effects. Currently, nearly 40% of UC patients are treated with herbal natural products in combination with traditional medications to reduce the incidence of toxic side effects. Flavonoid herbal natural products are the most widely distributed polyphenols in plants and fruits, which have certain antioxidant and anti-inflammatory activities. Flavonoid herbal natural products have achieved remarkable efficacy in the treatment of UC. The pharmacological mechanisms are related to anti-inflammation, promotion of mucosal healing, maintenance of intestinal immune homeostasis, and regulation of intestinal flora. In this paper, we summarize the flavonoid components of anti-ulcerative colitis and their mechanisms reported in the past 10 years, to provide a basis for rational clinical use and the development of new anti-ulcerative colitis drugs.

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Electroacupuncture ameliorates knee osteoarthritis in rats via inhibiting NLRP3 inflammasome and reducing pyroptosis.

Knee Osteoarthritis (KOA), is the most common joint disease worldwide. The pathogenesis of KOA is complex and electroacupuncture (EA) is an effective therapy for KOA, but the mechanism remains unclear. In this study, we aim to investigate the potential therapeutic effect of EA on the rat model of KOA induced by monosodium iodoacetate (MIA) and its relationship with NLRP3 inflammasome by immunohistochemistry and western blot.

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Application of multilevel models for predicting pain following root canal treatment.

This study developed predictive models for one-week acute and six-month persistent pain following root canal treatment (RCT). An additional aim was to study the gain in predictive efficacy of models containing clinical factors only, over models containing sociodemographic characteristics.

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Efficacy of the Digital Therapeutic sinCephalea in the prophylaxis of migraine in patients with episodic migraine: study protocol for a digital, randomized, open-label, standard treatment controlled trial.

The German government implemented the Digital Healthcare Act in order to bring Digital Therapeutics into standard medical care. This is one of the first regulatory pathways to reimbursement for Digital Therapeutics (DTx). The Digital Therapeutic sinCephalea is intended to act as a prophylactic treatment of migraine by reducing the migraine days. For this, sinCephalea determines personalized nutritional recommendations using continuous glucose monitoring (CGM) data and enables the patients to follow a personalized low-glycemic nutrition. Migraine is a headache disorder with the highest socioeconomic burden. Emerging evidence shows that CGM-based personalized nutritional recommendations are of prophylactic use in episodic migraine. However, prospective data are yet missing to demonstrate clinical effectiveness. This study is designed to fill this gap.

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Pre-incisional infiltration with ropivacaine plus dexamethasone palmitate emulsion for postoperative pain in patients undergoing craniotomy: study protocol for a prospective, randomized controlled trial.

Post-craniotomy pain is a common occurrence which is associated with poor outcomes. Pre-emptive scalp infiltration with dexamethasone and ropivacaine has been proven effective in previous studies but with limited clinical significance. Dexamethasone palmitate emulsion (D-PAL) is a pro-drug incorporating dexamethasone into lipid microspheres with greater anti-inflammatory activity and fewer side effects than free dexamethasone. However, its effects in post-craniotomy pain management remain unknown. This study hypothesizes that pre-emptive scalp infiltration with ropivacaine plus D-PAL emulsion can achieve superior analgesic effects to ropivacaine alone in adult patients undergoing craniotomy.

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