Auricular Acupuncture Prior to Menstruation Can Reduce Primary Dysmenorrhea: A Randomized Controlled Trial.

Objective: Primary dysmenorrhea is a common condition that impacts quality of life significantly. Auricular therapies have shown promise for treating primary dysmenorrhea, but there is a lack of evidence specifically for auricular acupuncture (AA). This study evaluated the safety and efficacy of AA for managing primary dysmenorrhea. Materials and Methods: A randomized, double-blinded controlled trial was conducted on 90 females with primary dysmenorrhea: an AA group; n = 45) and a sham-AA (SA) group; n = 45. Specific ear acupoints (i.e., Uterus, Endocrine, Shenmen, Subcortex, Liver, and Kidney) were used for the intervention, which was 1 or 2 days prior to the expected menstruation onset. Outcomes were visual analogue scale (VAS) scores, ibuprofen needs, and adverse events (AEs). Results: The AA group had significantly lower VAS scores, compared to the SA group at menstruation onset and for up to 12 hours (mean differences [MDs] and 95% confidence intervals [CIs]: -1.08 [-1.96, -0.21] and -1.17 [-2.16, -0.18], respectively). Both groups had reductions in pain levels, compared to the prior menstrual cycle; the AA group had a significantly greater improvement. The AA group needed fewer ibuprofen tablets (MD: -0.28; 95% CI: -0.58, 0.00]). AEs were mild pain and irritation at insertion sites, all resolved spontaneously with no lasting effects. Conclusions: AA is safe. It may be effective for managing primary dysmenorrhea. Further studies are warranted on AA's effectiveness in diverse populations and extended times.

Change in Skin Surface Temperature at the Posterior Neck When Using Acupuncture at Houxi Acupoint in Healthy Volunteers.

Introduction The use of acupuncture has been suggested for the treatment of neck pain. Recently, a large body of evidence demonstrated that acupuncture has an effect on microcirculation in pain regions, but the exact mechanism remains unclear. This study aims to evaluate the skin surface thermographic changes in the posterior neck associated with manual acupuncture at the Houxi (SI-3) acupoint. Methods Sixty healthy volunteers of both genders, aged 18 to 30 years, were randomly determined into two groups: left acupuncture (Group A) and right acupuncture (Group B). Each group underwent two sessions with a seven-day interval. The first session involved acupuncture at the control Yuji (LU-10) acupoint, while the second session featured acupuncture at the SI-3 acupoint. Skin temperature at the posterior neck was measured by using an infrared thermal camera (FLIR C5™, FLIR® Systems, Inc., Wilsonville, OR, USA) at five time points with 5-minute intervals. Results There were statistically significant increases in posterior neck skin surface temperature (p < 0.05) during acupuncture at both the left and right SI-3 acupoints, but no significant change was observed during acupuncture at the left and right LU-10 acupoints. Furthermore, acupuncture at the SI-3 acupoint on either hand increased posterior neck skin surface temperature without a statistically significant difference (p > 0.05). Conclusion We observed that applying acupuncture at the SI-3 acupoint increased the skin surface temperature of the posterior neck area. Furthermore, the SI-3 acupoint exhibits a uniform impact on the posterior neck area's skin surface temperature, regardless of the side chosen for acupuncture.

Thread-embedding acupuncture may improve symptom resolution in patients with gastroesophageal reflux disease: A randomized controlled trial.

Background: Various traditional medicine treatments have been investigated to treat GERD. Among those, thread-embedding acupuncture (TEA) has the advantage that patients need to undergo the procedure infrequently; however, its efficacy is unclear. This study evaluated the efficacy of TEA in treating GERD. Methods: A randomized controlled trial was conducted with 66 participants with GERD: 33 received two sessions of TEA + standard therapy (proton-pump inhibitor [PPI]) (TEA+PPI group) and 33 received PPI alone (PPI group). Primary outcomes included GerdQ score and heartburn and regurgitation resolution. Secondary outcomes were antacids requirement, the Frequency Scale for Symptoms of GERD (FSSG) score, and Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) score. The safety outcome was adverse events (AEs). Results: After four weeks of treatment, the TEA+PPI group significantly reduced the GerdQ score (mean difference [MD] and 95% confidence interval [CI]: -1.8 [-2.4, -1.1]) and increased the rate of heartburn and regurgitation resolution compared to PPI (54.5% versus 9.1%, respectively) compared to PPI. The TEA+PPI group also significantly reduced the number of antacid packs used (MD [95%-CI]: -9.4 [-12.1, -6.7]), FSSG score (MD [95%-CI]: -9.4 [-11.0, -7.8]), and GERD-HRQL score (MD [95%-CI]: -5.6 [-7.7, -3.5]) compared to PPI. Five patients experienced AEs, which were mild local complications at the acupoints. Conclusion: TEA combined with PPI is more effective than PPI alone in treating GERD. Further studies with longer follow-ups are required to confirm these findings. Clinical trials registration information: ClinicalTrials.gov, NCT05353933.

Heart rate variability during auricular acupressure at the left sympathetic point on healthy volunteers: a pilot study.

Introduction: This research is a pilot, single-blinded study investigating heart rate variability (HRV) during auricular acupressure at the left sympathetic point (AH7) in healthy volunteers. Methods: There were 120 healthy volunteers with hemodynamic indexes (heart rate, blood pressure) within normal ranges, randomly divided into two groups AG and SG (in each group having a gender ratio 1:1, aged 20-29), to receive either auricular acupressure using ear seed (AG) or sham method using adhesive patches without seed (SG) at the left sympathetic point while lying in a supine position. Acupressure intervention lasted 25 min, and HRV was recorded by a photoplethysmography device-namely, Kyto HRM-2511B and Elite appliance. Results: Auricular acupressure at the left Sympathetic point (AG) led to a significant reduction in heart rate (HR) (p < 0.05) and a considerable increase in HRV parameters demonstrated by HF (High-frequency power) (p < 0.05), compared to sham auricular acupressure (SG). However, no significant changes in LF (Low-frequency power) and RR (Respiratory rate) (p > 0.05) were observed in both groups during the process. Conclusion: These findings suggest that auricular acupressure at the left sympathetic point may activate the parasympathetic nervous system while a healthy person is lying relaxed.

Discovery of AcrAB-TolC pump inhibitors: Virtual screening and molecular dynamics simulation approach.

AcrAB-TolC tripartite efflux pump, which belongs to the RND superfamily, is a main multi-drug efflux system of Escherichia coli (E. coli) because of the broad resistance on various antibiotics. With the discovering of efflux pump inhibitors (EPIs), a combination between these and antibiotics is one of the most promising therapies. Therefore, building a virtual screening model with prediction capacities for the efflux pump inhibitory activities of candidates from DrugBank and ZINC15 dataset, is one of the key goals of this project. Based on the database of 170 diverse chemical structures collected from 28 research journals, two 2D-QSAR models and a 3D-pharmacophore model have been performed. On the AcrB protein (PDB 4DX7), two binding sites have been discovered that match to the hydrophobic trap in the distal pocket and the switch loop in the proximal pocket. After virtual screening processes, twenty candidate AcrAB-TolC inhibitors have been subjected to molecular dynamics simulations, binding free energy calculations and ADMET predictions. The results indicate that three compounds namely DB09233, DB02581, and DB15224 are potential inhibitors with ΔGbind of -42.30 ± 4.58, -40.76 ± 7.30 and -31.06 ± 7.63 kcal.mol-1, respectively.Communicated by Ramaswamy H. Sarma.

Identification of small molecules as potential inhibitors of interleukin 6: a multi-computational investigation.

IL(interleukin)-6 is a multifunctional cytokine crucial for immunological, hematopoiesis, inflammation, and bone metabolism. Strikingly, IL-6 has been shown to significantly contribute to the initiation of cytokine storm-an acute systemic inflammatory syndrome in Covid-19 patients. Recent study has showed that blocking the IL-6 signaling pathway with an anti-IL-6 receptor monoclonal antibody (mAb) can reduce the severity of COVID-19 symptoms and enhance patient survival. However, the mAb has several drawbacks, such as high cost, potential immunogenicity, and invasive administration due to the large-molecule protein product. Instead, these issues could be mitigated using small molecule IL-6 inhibitors, but none are currently available. This study aimed to discover IL-6 inhibitors based on the PPI with a novel camelid Fab fragment, namely 68F2, in a crystal protein complex structure (PDB ID: 4ZS7). The pharmacophore models and molecular docking were used to screen compounds from DrugBank databases. The oral bioavailability of the top 24 ligands from the screening was predicted by the SwissAMDE tool. Subsequently, the selected molecules from docking and MD simulation illustrated a promising binding affinity in the formation of stable complexes at the active binding pocket of IL-6. Binding energies using the MM-PBSA technique were applied to the top 4 hit compounds. The result indicated that DB08402 and DB12903 could form strong interactions and build stable protein-ligand complexes with IL-6. These potential compounds may serve as a basis for further developing small molecule IL-6 inhibitors in the future.

Telepharmacy: A Systematic Review of Field Application, Benefits, Limitations, and Applicability During the COVID-19 Pandemic.

Introduction: Telepharmacy is widely known as the delivery of pharmacy care offered by registered pharmacists and pharmacies using telecommunication technologies to patients at a distance. We conducted a systematic review of the reported usages, benefits, and limitations of telepharmacy models worldwide to further clarify the pros and cons of a telepharmacy model. Methods: A total of 39 relevant articles was included after searching for articles with a fixed term on four databases, including PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar, as of April 2021. Results: Our review suggested that telepharmacy has played an essential role in addressing pharmacist shortages and helping patients both safely and effectively administer medications in underserved areas. During the COVID-19 pandemic, remote dispensing and counseling are effective measures to avoid infection. Conclusion: Telepharmacy could potentially replace or complement pharmaceutical-related activities, facilitating future innovation in the health care industry.

Auricular Acupressure Effect on Autonomic Responses Evoked by a Cold Pressor Test in Healthy Volunteers: A Pilot Study.

Objective: This pilot study was conducted to investigate changes in the pulse rate and blood pressure in healthy volunteers after applying auricular acupressure at the "heart acupoint." Methods: A total of 120 healthy volunteers with hemodynamic indexes within normal limits were randomly allocated into 4 groups to receive auricular acupressure treatment either at the heart acupoint of the left or the right, or in both ears, and one control group without applying auricular acupressure. Results: Before the application of auricular acupressure, there were no statistical differences in pulse rate and blood pressure increments among the four groups during the first cold pressor test. In groups in which auricular pressure was applied, the pulse rate was significantly reduced after the application of auricular acupressure in three groups; however, no statistically significant difference was detected among the groups. Changes in blood pressure were not statistically significant in or among the different groups after applying auricular acupressure. The average recorded pulse rate values during the second cold pressor test (after auricular acupressure) were significantly lower compared to the corresponding values taken during the first cold pressor test (before auricular acupressure) (p < 0.05); however, pulse rate increments during the two cold pressor tests (with and without auricular acupressure) were similar (p > 0.05). Conclusions: These findings suggest that auricular acupressure could be used as an adjunctive nonpharmacological method for reducing the pulse rate.

Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study.

The World Health Organization declared monkeypox a global public health emergency on 23 July 2022. This disease was caused by the monkeypox virus (MPXV), which was first identified in 1958 in Denmark. The MPXV is a member of the Poxviridae family, the Chordopoxvirinae subfamily, and the genus Orthopoxvirus, which share high similarities with the vaccinia virus (the virus used to produce the smallpox vaccine). For the initial stage of infection, the MPXV needs to attach to the human cell surface glycosaminoglycan (GAG) adhesion molecules using its E8 protein. However, up until now, neither a structure for the MPXV E8 protein nor a specific cure for the MPXV exists. This study aimed to search for small molecules that inhibit the MPXV E8 protein, using computational approaches. In this study, a high-quality three-dimensional structure of the MPXV E8 protein was retrieved by homology modeling using the AlphaFold deep learning server. Subsequent molecular docking and molecular dynamics simulations (MDs) for a cumulative duration of 2.1 microseconds revealed that ZINC003977803 (Diosmin) and ZINC008215434 (Flavin adenine dinucleotide-FAD) could be potential inhibitors against the E8 protein with the MM/GBSA binding free energies of -38.19 ± 9.69 and -35.59 ± 7.65 kcal·mol-1, respectively.

Exploration of chalcones as 3-chymotrypsin-like protease (3CLpro) inhibitors of SARS-CoV-2 using computational approaches.

The main protease 3CLpro is one of the potential targets against coronavirus. Inhibiting this enzyme leads to the interruption of viral replication. Chalcone and its derivatives were reported to possess the ability to bind to 3CLpro protease in the binding pocket. This study explored an in-house database of 269 chalcones as 3CLpro inhibitors using in silico screening models, including molecular docking, molecular dynamics simulation, binding free energy calculation, and ADME prediction. C264 and C235 stand out as the two most potential structures. The top hit compound C264 was with the Jamda score of -2.8329 and the MM/GBSA binding energy mean value of -28.23 ± 3.53 kcal/mol, which was lower than the reference ligand. Despite the lower mean binding energy (-22.07 ± 3.39 kcal/mol), in-depth analysis of binding interaction suggested C235 could be another potential candidate. Further, in vitro and in vivo experiments are required to confirm the inhibitory ability. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02000-3.

Heart Rate Variability during Auricular Acupressure at Heart Point in Healthy Volunteers: A Pilot Study.

Heart rate variability (HRV) is the variation in time between each heartbeat. Increasing HRV may contribute to improving autonomic nervous system dysfunctions. Acupuncture stimulation through the vagus plexus in the ear is considered as a method that can improve HRV. In this pilot study, we examined 114 healthy volunteers at the Faculty of Traditional Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, from January to May 2020. During a 20-minute interval, participants were stimulated two times at the acupoint in the left ear with Semen seed. The heart rate and HRV values were monitored before, during, and after acupressure every 5 minutes. When we compared the experimental group with the control group, HRV significantly increased in the stage of ear-stimulated acupressure compared with the stage before and after the auricular acupressure (p=0.01, p=0.04, p=0.04 and p=0.02) and the difference was not statistically significant compared with the phase of nonstimulated (p=0.15, p=0.28). The changes in other values including SDNN (standard deviation of the average NN), RMSSD (root mean square of successive RR interval differences), LF (low-frequency power), and HF (high-frequency power) in all stages were not statistically significant (p=>0.05) between groups. Based on the results, we can determine the increase in HRV when conducting auricular acupressure with stimulation at the heart acupoint on the left ear. This leads to a direction in further studies for clinical application for patients with autonomic nervous disorder.

Structure-based 3D-Pharmacophore modeling to discover novel interleukin 6 inhibitors: An in silico screening, molecular dynamics simulations and binding free energy calculations.

Interleukin 6 (IL-6) is a cytokine with various biological functions in immune regulation, hematopoiesis, and inflammation. Elevated IL-6 levels have been identified in several severe disorders such as sepsis, acute respiratory distress syndrome (ARDS), and most recently, COVID-19. The biological activity of IL-6 relies on interactions with its specific receptor, IL-6Rα, including the membrane-bound IL-6 receptor (mIL-6R) and the soluble IL-6 receptor (sIL-6R). Thus, inhibition of the interaction between these two proteins would be a potential treatment for IL-6 related diseases. To date, no orally available small-molecule drug has been approved. This study focuses on finding potential small molecules that can inhibit protein-protein interactions between IL-6 and its receptor IL-6Rα using its crystal structure (PDB ID: 5FUC). First, two pharmacophore models were constructed based on the interactions between key residues of IL-6 (Phe74, Phe78, Leu178, Arg179, Arg182) and IL-6Rα (Phe229, Tyr230, Glu277, Glu278, Phe279). A database of approximately 22 million compounds was screened using 3D-pharmacophore models, molecular docking models, and ADMET properties. By analyzing the interactive capability of successfully docked compounds with important amino acids, 12 potential ligands were selected for further analysis via molecular dynamics simulations. Based on the stability of the complexes, the high interactions rate of each ligand with the key residues of IL-6/IL-6Rα, and the low binding free energy calculation, two compounds ZINC83804241 and ZINC02997430, were identified as the most potential IL-6 inhibitor candidates. These results will pave the way for the design and optimization of more specific compounds to combat cytokine storm in severe coronavirus patients.

Chalcone Derivatives as Potential Inhibitors of P-Glycoprotein and NorA: An In Silico and In Vitro Study.

The human P-glycoprotein (P-gp) and the NorA transporter are the major culprits of multidrug resistance observed in various bacterial strains and cancer cell lines, by extruding drug molecules out of the targeted cells, leading to treatment failures in clinical settings. Inhibiting the activity of these efflux pumps has been a well-known strategy of drug design studies in this regard. In this manuscript, our earlier published machine learning models and homology structures of P-gp and NorA were utilized to screen a chemolibrary of 95 in-house chalcone derivatives, identifying two hit compounds, namely, F88 and F90, as potential modulators of both transporters, whose activity on Staphylococcus aureus strains overexpressing NorA and resistant to ciprofloxacin was subsequently confirmed. The findings of this study are expected to guide future research towards developing novel potent chalconic inhibitors of P-gp and/or NorA.

Identification of potential interleukin-8 inhibitors acting on the interactive site between chemokine and CXCR2 receptor: A computational approach.

Interactions between interleukin (IL)-8 and its receptors, CXCR1, and CXCR2, serve crucial roles in inflammatory conditions and various types of cancers. Inhibition of this signaling pathway has been exploited as a promising strategy in treating these diseases. However, most studies only focused on the design of allosteric antagonists-bound receptors on the intracellular side of IL-8 receptors. Recently, the first cryo-EM structures of IL-8-CXCR2-Gi complexes have been solved, revealing the unique binding and activation modes of the endogenous chemokine IL-8. Hence, we set to identify small molecule inhibitors for IL-8 using critical protein-protein interaction between IL-8 and CXCR2 at the orthosteric binding site. The pharmacophore models and molecular docking screened compounds from DrugBank and NCI databases. The oral bioavailability of the top 23 ligands from the screening was then predicted by the SwissAMDE tool. Molecular dynamics simulation and free binding energy calculation were performed for the best compounds. The result indicated that DB14770, DB12121, and DB03916 could form strong interactions and stable protein-ligand complexes with IL-8. These three candidates are potential IL-8 inhibitors that can be further evaluated by in vitro experiments in the next stage.

Discovery of small molecular inhibitors for interleukin-33/ST2 protein-protein interaction: a virtual screening, molecular dynamics simulations and binding free energy calculations.

The interleukin-1 receptor like ST2 has emerged as a potential drug discovery target since it was identified as the receptor of the novel cytokine IL-33, which is involved in many inflammatory and autoimmune diseases. For the treatment of such IL-33-related disorders, efforts have been made to discover molecules that can inhibit the protein-protein interactions (PPIs) between IL-33 and ST2, but to date no drug has been approved. Although several anti-ST2 antibodies have entered clinical trials, the exploration of small molecular inhibitors is highly sought-after because of its advantages in terms of oral bioavailability and manufacturing cost. The aim of this study was to discover ST2 receptor inhibitors based on its PPIs with IL-33 in crystal structure (PDB ID: 4KC3) using virtual screening tools with pharmacophore modeling and molecular docking. From an enormous chemical space ZINC, a potential series of compounds has been discovered with stronger binding affinities than the control compound from a previous study. Among them, four compounds strongly interacted with the key residues of the receptor and had a binding free energy < - 20 kcal/mol. By intensive calculations using data from molecular dynamics simulations, ZINC59514725 was identified as the most potential candidate for ST2 receptor inhibitor in this study.

A novel nonsense mutation of ERCC2 in a Vietnamese family with xeroderma pigmentosum syndrome group D.

Xeroderma pigmentosum (XP) group D, a severe disease often typified by extreme sun sensitivity, can be caused by ERCC2 mutations. ERCC2 encodes an adenosine triphosphate (ATP)-dependent DNA helicase, namely XP group D protein (XPD). The XPD, one of ten subunits of the transcription factor TFIIH, plays a critical role in the nucleotide-excision repair (NER) pathway. Mutations in XPD that affect the NER pathway can lead to neurological degeneration and skin cancer, which are the most common causes of death in XP patients. Here, we present detailed phenotypic information on a Vietnamese family in which four members were affected by XP with extreme sun sensitivity. Genomic analysis revealed a compound heterozygous mutation of ERCC2 that affected family members and single heterozygous mutations in unaffected family members. We identified a novel, nonsense mutation in one allele of ERCC2 (c.1354C > T, p.Q452X) and a known missense mutation in the other allele (c.2048G > A, p.R683Q). Fibroblasts isolated from the compound heterozygous subject also failed to recover from UV-driven DNA damage, thus recapitulating aspects of XP syndrome in vitro. We describe a novel ERCC2 variant that leads to the breakdown of the NER pathway across generations of a family presenting with severe XP.

Anti-inflammatory and wound healing activities of calophyllolide isolated from Calophyllum inophyllum Linn.

Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP) compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines-IL-1ß, IL-6, TNF-α, but up-regulation of the anti-inflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.