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1.
Langenbecks Arch Surg ; 408(1): 391, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37814175

ABSTRACT

BACKGROUND: Optimal pain management is one of the core elements of Enhanced Recovery After Surgery (ERAS®) protocols and remains a challenge. Acupuncture (AC) is an effective treatment for various pain conditions. Systematic and personalized allocation of acupoints may be decisive for efficacy. METHODS: Based on the predominant pressure sensitivity of six gastrointestinal (GI) checkpoints (G1-G6), we devised a method to detect personalized patterns of pain and a corresponding set of acupoints. We performed a single AC treatment with semi-permanent needles and assessed the visual analogue scale (VAS) score, pain threshold based on pressure algometry (PA), and temperature changes on abdominal skin areas before and 5 min after AC. RESULTS: Between April and June 2021, thirty-eight patients were prospectively included in this pilot study. The mean reduction in subjective pain sensation as assessed by VAS was 86%, paralleled by an augmentation of the pain threshold as measured by PA by 64%. A small but significant increase in the skin temperature was observed above the abdominal surface. These effects were independent of the type of surgery. CONCLUSION: Checkpoint acupuncture may be a complementary tool for postoperative pain management. Further investigations are needed to explore this analgesic effect.


Subject(s)
Acupuncture Therapy , Humans , Pilot Projects , Pain, Postoperative/prevention & control , Pain Management , Pain Measurement
2.
Adv Mind Body Med ; 36(3): 4-11, 2022.
Article in English | MEDLINE | ID: mdl-36308504

ABSTRACT

Context: Qigong, a mind-body practice in traditional Chinese medicine (TCM), can improve cognitive functions, emotional balance, attention, multitask management, stress-coping, and well-being. One limitation of Qigong research is a lack of adequate controls. Objective: The current study intended to evaluate whether a single 5-min practice of a White Ball (WB) Qigong exercise could improve the perceptual auditory attention, divided and focused, in adults and whether obtaining potential effects would require a minimum level of training. Design: The research team designed a prospective, randomized, placebo-controlled, and single-blinded study. Setting: The study took place at the Institute of Biomedical Sciences (ICBAS) at the University of Porto in Porto, Portugal. Participants: Participants were 55 students at the University of Porto, 30 of whom were students attending the second year of medical school at ICBAS with no experience in Qigong and 25 of whom were students in the specialization and Master's programs in TCM with experience in Qigong. Intervention: The research team randomly distributed the 30 participants without experience into two groups, a negative control group (n = 15), who watched a wildlife video for 5 min in an orthostatic position, and a positive control group , the verum Qigong group (n = 15), who participated in 5 min of Qigong practice. The Qigong-practitioner group (n = 25), the intervention group, participated in the same 5-min Qigong, doing it with expertise. Outcome Measures: The study measured reaction time (RT) under two experimental conditions, one an auditory RT task and the second an auditory RT task with visual distraction. The procedure was constant for all the studied groups. Results: Postintervention, the reaction time (RT) in the negative control and the verum Qigong groups hadn't changed significantly (P > .05), while that of the Qigong-practitioner group had decreased significantly, with shorter RTs under the two experimental conditions, with P = .006 for the auditory RT and P = .003 for the auditory + visual distraction. Qigong may induce a conditioning effect that comes with regular practice. Conclusions: The WB Qigong had a positive effect on the AA mechanism, with a significant reduction in RT. The results support the importance of practice to achieve positive effects. People with neurodevelopmental disorders, such as autism and ADHD, struggle every day for sensory integration of AA mechanisms. Qigong can be taught and easily learned from the age of 2 years until senior ages, and it's a safe and very low-cost intervention that deserves to be researched further in clinical trials. These potential benefits of Qigong should be confirmed by future studies.


Subject(s)
Autism Spectrum Disorder , Qigong , Adult , Humans , Child, Preschool , Qigong/methods , Autism Spectrum Disorder/therapy , Prospective Studies , Single-Blind Method , Attention
3.
Invest New Drugs ; 39(3): 670-685, 2021 06.
Article in English | MEDLINE | ID: mdl-33313992

ABSTRACT

Background Precision medicine and drug repurposing are attractive strategies, especially for tumors with worse prognosis. Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing. Methods The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochemistry corroborated RNA-sequencing data. The expression of additional markers (AKT, SRC, mTOR, NF-κB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chemical library of > 1500 FDA-approved drugs and > 25,000 novel compounds in the ZINC database to find established drugs targeting BRAF47-438del and PIK3R1-G376R mutated proteins. Results Several compounds (including anthracyclines) bound with higher affinities than the control drugs (sorafenib and vemurafenib for BRAF and PI-103 and LY-294,002 for PIK3R1). Subsequent cytotoxicity analyses showed that anthracyclines might be suitable drug candidates. Aclarubicin revealed higher cytotoxicity than both sorafenib and vemurafenib, whereas idarubicin and daunorubicin revealed higher cytotoxicity than LY-294,002. Liposomal formulations of anthracyclines may be suitable to cross the blood brain barrier. Conclusions In conclusion, we identified novel small molecules via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.


Subject(s)
Antineoplastic Agents/therapeutic use , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Aged , Anthracyclines/pharmacology , Anthracyclines/therapeutic use , Antineoplastic Agents/pharmacology , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Line, Tumor , Class Ia Phosphatidylinositol 3-Kinase/genetics , Class Ia Phosphatidylinositol 3-Kinase/metabolism , Drug Repositioning , Genotype , Glioblastoma/genetics , Glioblastoma/metabolism , Humans , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , Temozolomide/pharmacology , Temozolomide/therapeutic use , Transcriptome
4.
BMC Neurol ; 18(1): 40, 2018 Apr 13.
Article in English | MEDLINE | ID: mdl-29653569

ABSTRACT

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus with significant clinical sequelae that can affect a patient's quality of life. Metabolic and microvascular factors are responsible for nerve damage, causing loss of nerve function, numbness, painful sensory symptoms, and muscle weakness. Therapy is limited to anti-convulsant or anti-depressant drugs for neuropathic pain and paresthesia. However, reduced sensation, balance and gait problems are insufficiently covered by this treatment. Previous data suggests that acupuncture, which has been in use in Traditional Chinese Medicine for many years, may potentially complement the treatment options for peripheral neuropathy. Nevertheless, more objective data on clinical outcome is necessary to generally recommend acupuncture to the public. METHODS: We developed a study design for a prospective, randomized (RCT), placebo-controlled, partially double-blinded trial for investigating the effect of acupuncture on DPN as determined by nerve conduction studies (NCS) with the sural sensory nerve action potential amplitude as the primary outcome. The sural sensory nerve conduction velocity, tibial motor nerve action potential amplitude, tibial motor nerve conduction velocity, the neuropathy deficit score, neuropathy symptom score, and numeric rating scale questionnaires are defined as secondary outcomes. One hundred and eighty patients with type 2 diabetes mellitus will be randomized into three groups (needle acupuncture, verum laser acupuncture, and placebo laser acupuncture). We hypothesize that needle and laser acupuncture have beneficial effects on electrophysiological parameters and clinical and subjective symptoms in relation to DPN in comparison with placebo. DISCUSSION: The ACUDIN trial aims at investigating whether classical needle acupuncture and/or laser acupuncture are efficacious in the treatment of DPN. For the purpose of an objective parameter, NCS were chosen as outcome measures. Acupuncture treatment may potentially improve patients' quality of life and reduce the socio-economic burden caused by DPN. TRIAL REGISTRATION: German Clinical Trial Register (DRKS), No. DRKS00008562 , trial search portal of the WHO ( http://apps.who.int/trialsearch/ ).


Subject(s)
Acupuncture Therapy , Diabetes Mellitus, Type 2/therapy , Diabetic Neuropathies/therapy , Humans , Randomized Controlled Trials as Topic
5.
Pharmacol Res ; 110: 216-226, 2016 08.
Article in English | MEDLINE | ID: mdl-26902577

ABSTRACT

Schistosomiasis is a helminthic disease affecting more than 200 million people in the tropics as well as returning travellers. Treatment mainly relies on a single drug, praziquantel. Praziquantel cannot kill developing schistosomula resulting in frequent treatment failures and re-infections. Monotherapy also favors the selection for resistance. New drugs are therefore urgently needed. The activity of the semi-synthetic artemisinin derivatives artemether, artesunate and arteether is not restricted to malaria. We reviewed their anti-schistosomal activity in vivo and in patients by searching the PubMed database for publications since 1983 with the search terms "artemisinin" and "Schistosoma". Reports on in vivo studies in animals and clinical trials in human beings were selected. S. mansoni, S. japonicum, and S. haematobium have been tested in mice, rabbits, hamsters, and dogs. These artemisinin derivatives strongly reduced total worm rates with stronger reduction rates for female worms than for males. The drugs also reduced egg burden and egg-caused granulomata in the host liver. Artemisinin-type drugs induced oxidative and metabolic stress leading to morphological damage and decreased fertility of the parasites. Although artemether and artesunate have been investigated in numerous clinical trials, the poor quality of many has led to inconsistent results and has not provided convincing evidence on the therapeutic value against schistosomiasis. Despite these methodological concerns, clinical trials may indicate anti-schistosomal activity in patients. Convincing clinical trials providing unambiguous evidence are now needed. Furthermore, suitable treatment protocols for combination therapy to prevent/treat praziquantel-resistant Schistosoma strains should be investigated.


Subject(s)
Artemisinins/pharmacology , Artemisinins/therapeutic use , Schistosoma/drug effects , Schistosomiasis/drug therapy , Schistosomicides/therapeutic use , Animals , Artemether , Artemisinins/chemical synthesis , Artesunate , Female , Humans , Male , Parasite Egg Count , Schistosoma/pathogenicity , Schistosomiasis/diagnosis , Schistosomiasis/parasitology , Schistosomicides/chemical synthesis , Treatment Outcome
6.
Molecules ; 21(4): 496, 2016 Apr 15.
Article in English | MEDLINE | ID: mdl-27092478

ABSTRACT

Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS oncogenes and the slow proliferative activity in terms of cell doubling times significantly correlated with scopoletin resistance. COMPARE and hierarchical cluster analyses of transcriptome-wide mRNA expression resulted in a set of 40 genes, which all harbored binding motifs in their promoter sequences for the transcription factor, NF-κB, which is known to be associated with drug resistance. RAS mutations, slow proliferative activity, and NF-κB may hamper its effectiveness. By in silico molecular docking studies, we found that scopoletin bound to NF-κB and its regulator IκB. Scopoletin activated NF-κB in a SEAP-driven NF-κB reporter cell line, indicating that NF-κB might be a resistance factor for scopoletin. In conclusion, scopoletin might serve as lead compound for drug development because of its favorable activity against tumor cells with ABC-transporter expression, although NF-κB activation may be considered as resistance factor for this compound. Further investigations are warranted to explore the full therapeutic potential of this natural product.


Subject(s)
Drug Resistance, Neoplasm/genetics , NF-kappa B/biosynthesis , Neoplasms/drug therapy , Plant Extracts/administration & dosage , Scopoletin/administration & dosage , ATP-Binding Cassette Transporters/biosynthesis , ATP-Binding Cassette Transporters/genetics , Artemisia/chemistry , Cell Line, Tumor , Drug Resistance, Multiple , Gene Expression Regulation, Neoplastic/drug effects , Humans , Molecular Docking Simulation , NF-kappa B/genetics , Neoplasms/genetics , Pharmacogenetics , Plant Extracts/chemistry , Protein Array Analysis , Scopoletin/chemistry , Signal Transduction/drug effects , Transcription Factor RelA/biosynthesis
7.
Med Probl Perform Art ; 31(1): 8-12, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26966958

ABSTRACT

BACKGROUND: Owing to repetitive movements and a very stressful and competitive lifestyle, musicians are a group that may be prone to suffer from occupational diseases. According to the literature, musicians are affected mainly by two types of occupational diseases: music performance anxiety (MPA) and playing-related musculoskeletal disorders (PRMDs). The aim of this study was to describe the prevalence of the most common complaints affecting musicians in the three professional orchestras from northern Portugal. METHODS: Professional orchestra musicians (n=112) from the three main professional orchestras from northern Portugal were individually interviewed about their physical and psychological complaints. RESULTS: Results indicated that 94% of musicians interviewed self-reported at least one working-related problem. PRMDs were the most common conditions, affecting 84.8% of musicians. The most affected areas were the shoulder and the cervical and lumbar regions. MPA was reported by 13.2% of musicians. CONCLUSION: The present work covers about 50% of all Portuguese professional orchestra musicians. It raises awareness of the importance of focusing on the high prevalence of professional diseases among musicians.


Subject(s)
Musculoskeletal Pain/epidemiology , Music , Occupational Diseases/epidemiology , Occupational Health/statistics & numerical data , Adult , Female , Health Status , Humans , Male , Middle Aged , Occupational Injuries/epidemiology , Portugal , Risk Factors , Severity of Illness Index , Young Adult
8.
Invest New Drugs ; 33(2): 513-20, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25637166

ABSTRACT

Aptamers are short single-stranded DNA or RNA oligonucleotides that are capable of binding small molecules, proteins, or nucleotides with high specificity. They show a stable conformation and high binding affinity for their target molecules. There are numerous applications for aptamers in biotechnology, molecular diagnostics and targeted therapy of diseases. Their production is cheap, and they generally display lower immunogenicity than monoclonal antibodies. In the present review, we give an introduction to the preparation of aptamers and provide examples for their use in biotechnology, diagnostics and therapy of diseases.


Subject(s)
Aptamers, Nucleotide/chemistry , Biomedical Research/methods , Diagnostic Techniques and Procedures , Biomarkers , Cellular Reprogramming Techniques , Chromatography, Affinity , DNA, Single-Stranded , Gene Library , Humans , Substance Abuse Detection
9.
Invest New Drugs ; 33(1): 32-44, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25342140

ABSTRACT

Ergot alkaloids are psychoactive and vasoconstricting agents of the fungus Claviceps purpurea causing poisoning such as ergotism in medieval times (St. Anthony's Fire). This class of substances also inhibits tumor growth in vitro and in vivo, though the underlying mechanisms are unclear as yet. We investigated six ergot alkaloids (agroclavine, ergosterol, ergocornin E, ergotamine, dihydroergocristine, and 1-propylagroclavine tartrate) for their cytotoxicity towards tumor cell lines of the National Cancer Institute, USA. 1-Propylagroclavine tartrate (1-PAT) revealed the strongest cytotoxicity. Out of 76 clinically established anticancer drugs, cross-resistance was found between the ergot alkaloids and 6/7 anti-hormonal drugs (=85.7 %) and 5/15 DNA-alkylating drugs (=33.3 %). The IC50 values for the six alkaloids were not correlated to well-known determinants of drug resistance, such as proliferative activity (as measured by cell doubling times, PCNA expression, and cell cycle distribution), the multidrug resistance-mediating P-glycoprotein/MDR1 and expression or mutations of oncogenes and tumor suppressor genes (EGFR, RAS, TP53). While resistance of control drugs (daunorubicin, cisplatin, erlotinib) correlated with these classical resistance mechanisms, ergot alkaloids did not. Furthermore, COMPARE and hierarchical cluster analyses were performed of mRNA microarray data to identify genes correlating with sensitivity or resistance to 1-PAT. Twenty-three genes were found with different biological functions (signal transducers, RNA metabolism, ribosome constituents, cell cycle and apoptosis regulators etc.). The expression of only 3/66 neuroreceptor genes correlated with the IC50 values for 1-PAT, suggesting that the psychoactive effects of ergot alkaloids may not play a major role for the cytotoxic activity against cancer cells. In conclusion, the cytotoxicity of ergot alkaloids is not involved in classical mechanisms of drug resistance opening the possibility to bypass resistance and to treat otherwise drug-resistant and refractory tumors. The modes of action are multifactorial, which is a typical feature of many natural compounds.


Subject(s)
Antineoplastic Agents/pharmacology , Ergot Alkaloids/pharmacology , Neoplasms/drug therapy , Cell Line, Tumor , Cell Survival/drug effects , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic/drug effects , Humans , Microarray Analysis , Neoplasms/genetics , RNA, Messenger/genetics
10.
Nutr Cancer ; 67(4): 664-75, 2015.
Article in English | MEDLINE | ID: mdl-25837780

ABSTRACT

The frequent failure of standard cancer chemotherapy requires the development of novel drugs capable of killing otherwise drug-resistant tumors. Here, we have investigated a chloroform extract of Laurus nobilis seeds. Fatty acids and 23 constituents of the volatile fraction were identified by gas chromotography/flame ionization detection (GC/FID) and gas chromatography/mass spectrometry (GC/MS), in good agreement with (1)H NMR (nuclear magnetic resonance) spectrum. Multidrug-resistant P-glycoprotein-expressing CEM/ADR5000 leukemia cells were hypersensitive (collaterally sensitive) toward this extract compared to drug-sensitive CCRF-CEM cells, whereas CEM/ADR5000 cells were 2586-fold resistant to doxorubicin as control drug. Collateral sensitivity was verified by measurement of apoptotic cells by flow cytometry. The log10IC50 values of 3 compounds in the extract (limonene, eucalyptol, oleic acid) did not correlate with mRNA expression of the P-glycoprotein-coding ABCB1/MDR1 gene and accumulation of the P-glycoprotein substrate rhodamine in the NCI panel of tumor cell lines. A microarray-based profile of 20 genes predicted resistance to doxorubicin and 7 other anticancer drugs involved in the multidrug resistance phenotype but not to limonene, eucalyptol and oleic acid. In conclusion, our results show that Laurus nobilis seed extract is suitable to kill multidrug-resistant P-glycoprotein expressing tumor cells.


Subject(s)
Drug Resistance, Neoplasm , Laurus/chemistry , Plant Extracts/pharmacology , Seeds/chemistry , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Doxorubicin/pharmacology , Gas Chromatography-Mass Spectrometry , Humans , Leukemia/pathology
11.
Front Med (Lausanne) ; 11: 1371056, 2024.
Article in English | MEDLINE | ID: mdl-38476441

ABSTRACT

Background: Globally, diabetes mellitus (DM) and peripheral artery disease (PAD) have an increasing incidence and a high prevalence and are both associated with high morbidity and complication rates, e.g., as chronic non-healing peripheral ulcers. Impaired macro- and microcirculation and peripheral neuropathy lead to an increased risk of foot ulcers and infections. These complications are difficult to treat, have a high risk of becoming chronic and often lead to lower limb amputation. The aim of this planned study was to investigate the potential effects of acupuncture on improving microcirculation in patients with Diabetic Foot Syndrome (DFS) and PAD. Materials and methods: In 18 patients with chronic non-healing peripheral ulcers and diagnosed DM or PAD, data on 8 microcirculatory parameters were collected simultaneously on intact skin close to the wound margin. Microcirculation was assessed using an O2C device combining laser Doppler shift and white light spectroscopy (LEA Medizintechnik GmbH, Giessen, Germany). Unilateral and bilateral acupuncture was performed on the connecting line between acupuncture points Stomach 14 and Stomach 15. Results: After unilateral acupuncture (ipsilateral to the wound side), a statistically significant improvement in 7 out of 8 microcirculatory parameters was demonstrated compared to baseline measurements before acupuncture. After bilateral acupuncture, there was an additional improvement and statistical significance in all parameters in both DFS and PAD patients. Discussion: These results show an improvement in the microcirculation and peripheral blood flow at the edges of the wound. As impaired micro- and macrocirculation is considered to be a critical prognostic factor for the healing of a peripheral lesion, the intervention could have a positive impact on the healing of (chronic) peripheral wounds.

12.
Healthcare (Basel) ; 11(3)2023 Jan 19.
Article in English | MEDLINE | ID: mdl-36766882

ABSTRACT

The recent COVID-19 pandemic has increased students' stress as they may feel under increased pressure to have a good performance and compensate for the disruption to their education. Improving attention levels and learning capacity may assist in ameliorating academic performance. Qigong is a traditional Chinese medicine technique that appears to have positive effects on the management of mental health and may provide tools for coping with stressful situations. This paper explores data obtained while conducting a previous study and includes an excess of data from a total of 44 participants who were previously divided into an experimental Qigong group and a sham Qigong control group. The improvements in specific auditory processing and reaction times may indicate benefits in attention and learning capacity. These improvements were more pronounced in the experimental Qigong group compared to the sham Qigong group. Qigong may be able to assist in improving students' academic performance and can be easily integrated into physical education classes. It could also assist students to cope with the increased academic pressure resulting from the COVID-19 pandemic context.

13.
Obes Surg ; 33(7): 2176-2185, 2023 07.
Article in English | MEDLINE | ID: mdl-37246204

ABSTRACT

BACKGROUND: It remains challenging in clinical practice to perform optimal pain management following bariatric surgeries. Acupuncture (AC) is an effective method of postoperative pain management, but its clinical efficacy depends on the rationale used to select AC points. METHODS: We developed a method to identify individual patterns of pain and a corresponding set of acupoints (corrAC) based on the relative pressure sensitivity of six abdominal visceral pressure points, i.e., the gastrointestinal (GI) checkpoints (G1-G6). Patients with moderate to severe pain were included and received a single AC treatment following surgery. The visual analog scale (VAS) score, pain threshold, and skin temperature were assessed before AC and at 5 min, 1 h, and 24 h following AC. AC was performed with 1-mm-deep permanent needles. RESULTS: From April 2021 to March 2022, 72 patients were included in the analysis. Fifty-nine patients received corrAC, whereas 13 received a noncorresponding AC (nonAC) as an internal control. Patients receiving corrAC showed a significant reduction (74%) in pain at 5 min after treatment (p < 0.0001) and a significant increase (37%) in the pain threshold (p < 0.0001). In this group, a significant increase in skin temperature above G1, G3, G4, and G5 was observed. Patients receiving nonAC showed neither significant pain reduction nor significant changes in pain threshold. The skin above G3 and G4 did not reveal temperature changes. CONCLUSION: Checkpoint AC may be an effective tool in postoperative pain therapy after bariatric surgery. Vegetative functional involvement might be associated with pain relief.


Subject(s)
Acupuncture Therapy , Bariatric Surgery , Laparoscopy , Obesity, Morbid , Humans , Pilot Projects , Obesity, Morbid/surgery , Pain, Postoperative/drug therapy
14.
Comput Biol Med ; 157: 106781, 2023 05.
Article in English | MEDLINE | ID: mdl-36931205

ABSTRACT

RNA-sequencing has been proposed as a valuable technique to develop individualized therapy concepts for cancer patients based on their tumor-specific mutational profiles. Here, we aimed to identify drugs and inhibitors in an individualized therapy-based drug repurposing approach focusing on missense mutations for 35 biopsies of cancer patients. The missense mutations belonged to 9 categories (ABC transporter, apoptosis, angiogenesis, cell cycle, DNA damage, kinase, protease, transcription factor, tumor suppressor). The highest percentages of missense mutations were observed in transcription factor genes. The mutational profiles of all 35 tumors were subjected to hierarchical heatmap clustering. All 7 leukemia biopsies clustered together and were separated from solid tumors. Based on these individual mutation profiles, two strategies for the identification of possible drug candidates were applied: Firstly, virtual screening of FDA-approved drugs based on the protein structures carrying particular missense mutations. Secondly, we mined the Drug Gene Interaction (DGI) database (https://www.dgidb.org/) to identify approved or experimental inhibitors for missense mutated proteins in our dataset of 35 tumors. In conclusion, our approach based on virtual drug screening of FDA-approved drugs and DGI-based inhibitor selection may provide new, individual treatment options for patients with otherwise refractory tumors that do not respond anymore to standard chemotherapy.


Subject(s)
Neoplasms , Transcriptome , Humans , Drug Evaluation, Preclinical , Drug Repositioning , Early Detection of Cancer , Neoplasms/drug therapy , Neoplasms/genetics , Transcription Factors/genetics
15.
Comput Biol Med ; 133: 104359, 2021 06.
Article in English | MEDLINE | ID: mdl-33845270

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a major threat worldwide due to its fast spreading. As yet, there are no established drugs available. Speeding up drug discovery is urgently required. We applied a workflow of combined in silico methods (virtual drug screening, molecular docking and supervised machine learning algorithms) to identify novel drug candidates against COVID-19. We constructed chemical libraries consisting of FDA-approved drugs for drug repositioning and of natural compound datasets from literature mining and the ZINC database to select compounds interacting with SARS-CoV-2 target proteins (spike protein, nucleocapsid protein, and 2'-o-ribose methyltransferase). Supported by the supercomputer MOGON, candidate compounds were predicted as presumable SARS-CoV-2 inhibitors. Interestingly, several approved drugs against hepatitis C virus (HCV), another enveloped (-) ssRNA virus (paritaprevir, simeprevir and velpatasvir) as well as drugs against transmissible diseases, against cancer, or other diseases were identified as candidates against SARS-CoV-2. This result is supported by reports that anti-HCV compounds are also active against Middle East Respiratory Virus Syndrome (MERS) coronavirus. The candidate compounds identified by us may help to speed up the drug development against SARS-CoV-2.


Subject(s)
COVID-19 , Severe acute respiratory syndrome-related coronavirus , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , SARS-CoV-2 , Supervised Machine Learning
16.
Article in English | MEDLINE | ID: mdl-34199174

ABSTRACT

Practices such as "Reiki", therapeutic touch, healing touch, and external "Qigong" have been regarded as some form of "energy medicine" or "biofield therapy". The biofield concept has been studied and debated by researchers of distinct areas of expertise, and although the phenomenon was sometimes described as physically related to electromagnetics, other factors such as "subtle energy" and focused intention might be involved. These nonconventional practices integrate contact and non-contact techniques, and those dealing with so-called distant healing interventions are perhaps the most difficult to understand and accept. Practitioners describe these so-called nonlocal interventions as involving intentional factors and particular states of consciousness. With a spiritual mindset and a particular state of awareness, compassion is said to work out as a catalyst to produce physiological and physical changes through mechanisms that are still unknown. At the body level, these vegetative changes might be related to individual self-perception variations as part of the body neurovegetative feedback system of regulation. Further mechanisms are difficult to document and measure, and might be more accessible to research by using physical signal detectors, chemical dynamics methods, detectors using biological materials, detectors using living sensors, and detectors using the human body. The growing interest in these practices and the considerable amount of research exploring their effects and clinical applications encouraged this narrative review, which aims to provide an easy to consult partial overview of the history, theory and findings of quantitative research strategies exploring non-contact biofield-based practices. This work also aims to stimulate the reader's mind with the raised hypotheses, catalyzing further research on the subject to confirm or deny the reported outcomes.


Subject(s)
Mind-Body Therapies , Qigong , Consciousness , Electromagnetic Phenomena , Humans , Intention
17.
Healthcare (Basel) ; 9(3)2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33804485

ABSTRACT

Traditional Chinese medicine (TCM) is a systematic healthcare system developed from clinical experience based on a scientific model of regulation. TCM relies on unique theories and practices to treat diseases and enhance health. These practices include Chinese herbal medicine and dietetics, acupuncture and moxibustion, and other non-medication therapies such as Chinese bodywork or manual therapy, known as "Tuina", and traditional biofeedback exercises, known as "Qigong" and "Taijiquan". The integration of TCM in Western health systems and research requires a rational communicable theory, scientific proof of efficacy and safety, and quality control measures. Understanding the structural concepts of the TCM language makes possible the parallelism to Western physiology, and the inherent rational use of the reflex therapeutic systems, anti-inflammatory mechanisms and mental training involved, for example, in acupuncture and "Qigong". The results of TCM clinical trials and fundamental research on its nature and mechanisms have encouraged the development and application of well-designed research strategies such as double blinding in acupucture to overcome limitations and resistances in integrating these practices into the existing biomedical paradigms of the West. This review aims to overview some TCM theoretical concepts and the evidence-based clinical application of TCM's leading practices to create an easy-to-consult and condensed source of information, available for the healthcare community, facilitating the understanding and communication between conventional health professionals and TCM practitioners and acupuncturists.

18.
Healthcare (Basel) ; 9(2)2021 Feb 07.
Article in English | MEDLINE | ID: mdl-33562368

ABSTRACT

The integration of Traditional Chinese Medicine (TCM) in Western health systems and research requires a rational communicable theory, scientific proof of efficacy and safety, and quality control measures. The existence of clear definitions and the diagnosis standardization are critical factors to establish the patient's vegetative functional status accurately and, therefore, systematically apply TCM therapeutics such as the stimulation of reflex skin areas known as acupoints. This science-based conceptualization entails using validated methods, or even developing new systems able to parameterize the diagnosis and assess TCM related effects by objective measurements. Traditionally, tongue and pulse diagnosis and the functional evaluation of action points by pressure sensitivity and physical examination may be regarded as essential diagnostic tools. Parameterizing these techniques is a future key point in the objectification of TCM diagnosis, such as by electronic digital image analysis, mechanical pulse diagnostic systems, or the systematic evaluation of acupoints' electrophysiology. This review aims to demonstrate and critically analyze some achievements and limitations in the clinical application of device-assisted TCM diagnosis systems to evaluate functional physiological patterns. Despite some limitations, tongue, pulse, and electrophysiological diagnosis devices have been reported as a useful tool while establishing a person's functional status.

19.
J Bodyw Mov Ther ; 26: 309-317, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33992264

ABSTRACT

INTRODUCTION: Acupoints have bioelectrical properties distinct from common skin. Besides the higher electrical conductivity and lower resistance, acupoints show capacitor-like properties, which can be related to their endogenous electrical potential. Traditional Chinese Medicine (TCM) postulates that meridians are physiological structures connecting acupoints and working as a conduit for the flow of two essential substances known as qi and xue. OBJECTIVES: This pilot study was focused in evaluating whether the electrical potential of acupoints can be correlated objectively to the functional properties as described by ancient Chinese medical theories, such as the theories of coupled meridians of the same phase ('elements'), and the principle of coupled points. METHODS: Direct needle moxibustion on LU5 and needle dispulsion of LI4 were performed in 21 subjects. The electrical potential of each acupoint was measured with a high-resolution data acquisition system taking to reference the acupoint SP6 of the Spleen conduit. RESULTS: The results may indicate a functional relationship between the therapeutics and the electrical potential response on the selected acupoints. These effects seem to be explainable considering the specific properties of each acupoint, the relationship between TCM phases, and the dynamics between coupled conduits. CONCLUSION: The evaluation of the endogenous electrical potential of acupoints and the changes caused by an external stimulus might contribute to the understanding of TCM concepts, mechanisms, and the effects of associated therapeutics. The observed phenomena encourage the systematic assessment of the functional vegetative status via skin electrophysiology and using objective measurements.


Subject(s)
Acupuncture Therapy , Meridians , Moxibustion , Acupuncture Points , Data Analysis , Humans , Pilot Projects
20.
Mediators Inflamm ; 2010: 194896, 2010.
Article in English | MEDLINE | ID: mdl-20652055

ABSTRACT

INTRODUCTION: The Chinese extract Rhizoma coptidis is well known for its anti-inflammatory, antioxidative, antiviral, and antimicrobial activity. The exact mechanisms of action are not fully understood. METHODS: We examined the effect of the extract and its main compound, berberine, on LPS-induced inflammatory activity in a murine macrophage cell line. RAW 264.7 cells were stimulated with LPS and incubated with either Rhizoma coptidis extract or berberine. Activation of AP-1 and NFkappaB was analyzed in nuclear extracts, secretion of MCP-1/CCL2 was measured in supernatants. RESULTS: Incubation with Rhizoma coptidis and berberine strongly inhibited LPS-induced monocyte chemoattractant protein (MCP)-1 production in RAW cells. Activation of the transcription factors AP-1 and NFkappaB was inhibited by Rhizoma coptidis in a dose- and time-dependent fashion. CONCLUSIONS: Rhizoma coptidis extract inhibits LPS-induced MCP-1/CCL2 production in vitro via an AP-1 and NFkappaB-dependent pathway. Anti-inflammatory action of the extract is mediated mainly by its alkaloid compound berberine.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Chemokine CCL2/biosynthesis , Drugs, Chinese Herbal/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Macrophages/drug effects , NF-kappa B/physiology , Transcription Factor AP-1/physiology , Animals , Berberine/pharmacology , Cells, Cultured , Coptis chinensis , Interleukin-12/biosynthesis , Interleukin-1beta/biosynthesis , Macrophages/metabolism , Mice , Nitric Oxide/biosynthesis , Reactive Oxygen Species/metabolism
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