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International Journal of Molecular... Sep 2022Conventional cancer treatment is mainly based on the surgical removal of the tumor followed by radiotherapy and/or chemotherapy. When surgical removal is not possible,... (Review)
Review
Conventional cancer treatment is mainly based on the surgical removal of the tumor followed by radiotherapy and/or chemotherapy. When surgical removal is not possible, radiotherapy and, less often, chemotherapy is the only way to treat patients. However, despite significant progress in understanding the molecular mechanisms of carcinogenesis and developments in modern radiotherapy techniques, radiotherapy (alone or in combination) does not always guarantee treatment success. One of the main causes is the radioresistance of cancer cells. Increasing the radiosensitivity of cancer cells improves the processes leading to their elimination during radiotherapy and prolonging the survival of cancer patients. In order to enhance the effect of radiotherapy in the treatment of radioresistant neoplasms, radiosensitizers are used. In clinical practice, synthetic radiosensitizers are commonly applied, but scientists have recently focused on using natural products (phytocompounds) as adjuvants in radiotherapy. In this review article, we only discuss naturally occurring radiosensitizers currently in clinical trials (paclitaxel, curcumin, genistein, and papaverine) and those whose radiation sensitizing effects, such as resveratrol, have been repeatedly confirmed by many independent studies.
Topics: Biological Products; Curcumin; Genistein; Humans; Neoplasms; Paclitaxel; Papaverine; Radiation Tolerance; Radiation, Ionizing; Radiation-Sensitizing Agents; Resveratrol
PubMed: 36142554
DOI: 10.3390/ijms231810627 -
Scientific Reports Sep 2022Adenosine occasionally results in overestimation of fractional flow reserve (FFR) values, compared with other hyperemic stimuli. We aimed to elucidate the association of...
Adenosine occasionally results in overestimation of fractional flow reserve (FFR) values, compared with other hyperemic stimuli. We aimed to elucidate the association of overestimation of FFR by adenosine with anatomically significant but functionally non-significant lesions (anatomical-functional mismatch) and its influence on reclassification of functional significance. Distal-to-aortic pressure ratio (Pd/Pa) was measured using adenosine (Pd/Pa) and papaverine (Pd/Pa) in 326 patients (326 vessels). The overestimation of FFR was calculated as Pd/Pa-Pd/Pa. The anatomical-functional mismatch was defined as diameter stenosis > 50% and Pd/Pa > 0.80. Reclassification was indicated by Pd/Pa > 0.80 and Pd/Pa ≤ 0.80. The mismatch (n = 72) had a greater overestimation of FFR than the non-mismatch (n = 99): median 0.02 (interquartile range 0.01-0.05) versus 0.01 (0.00-0.04), p = 0.014. Multivariable analysis identified the overestimation of FFR (p = 0.003), minimal luminal diameter (p = 0.001), and non-left anterior descending artery (LAD) location (p < 0.001) as determinants of the mismatch. Reclassification was indicated in 29% of the mismatch and was more frequent in the LAD than in the non-LAD (52% vs. 20%, p = 0.005). The overestimation of FFR is an independent determinant of anatomical-functional mismatch. Anatomical-functional mismatch, specifically in the LAD, may suggest a false-negative result.
Topics: Adenosine; Cardiac Catheterization; Coronary Angiography; Coronary Stenosis; Coronary Vessels; Fractional Flow Reserve, Myocardial; Humans; Predictive Value of Tests; Severity of Illness Index
PubMed: 36056128
DOI: 10.1038/s41598-022-19330-1 -
Frontiers in Pharmacology 2022This present study aims to delineate crude extract (Rd.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rd.n-Hex, Rd.ETAC, and Rd.Aq), and emodin for antidiarrheal,...
This present study aims to delineate crude extract (Rd.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rd.n-Hex, Rd.ETAC, and Rd.Aq), and emodin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti-, antiulcer effects, and toxicology. Plant extracts attributed dose-dependent protection against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance transverse by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, it causes a concentration-dependent relaxation of both spontaneous and K (80 mM)-induced contraction, Rd.n-Hex and verapamil were relatively potent against K-induced contractions and shifted the Ca concentration-response curves (CRCs) to the right, Rd.Cr and Rd.ETAC shifted the isoprenaline-induced inhibitory CRCs to the left, showing potentiating effect similar to papaverine. Rd.n-Hex showed anti- effect. Extracts and emodin also show an inhibitory effect against H/K-ATPase. showed a gastroprotective and antioxidant effect. Histopathological evaluation showed improvement in cellular architecture and decrease in the expression of inflammatory markers such as cyclooxygenase (COX2), tumor necrosis factor (TNF-α), and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry, ELISA, and western blot techniques. In RT-PCR, it decreases H/K-ATPase mRNA levels. was analyzed for certain safety aspects and exhibited a relative safety profile as no impairment was observed in kidneys, heart, liver, and brain further assisted by biochemical and hematological analysis. Docking studies revealed that emodin against H/K-ATPase pump and voltage gated L-type calcium channel showed E-value of -7.9 and -7.4 kcal/mol, respectively. MD simulations and molecular mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area MMPBSA/GBSA findings are consistent with the and docking results. In conclusion, extracts and its phytoconstituent could be considered a potent antioxidant and anti-inflammatory drug candidates that possess anti-diarrheal, anti-secretary, antispasmodic, anti- and anti-ulcer potential. Toxicity studies were done according to OECD standards 425. It belongs to group 5 (LD50 > 2000 mg/kg), which suggests that it is in the lower toxicity class.
PubMed: 36052146
DOI: 10.3389/fphar.2022.936161 -
Urology Nov 2022To evaluate the usefulness of Power Doppler to improve the diagnostic work up of veno-occlusive erectile dysfunction patients.
OBJECTIVE
To evaluate the usefulness of Power Doppler to improve the diagnostic work up of veno-occlusive erectile dysfunction patients.
MATERIALS AND METHODS
Patients affected by erectile dysfunction, mean IIEF 5 = 13.5 (12-17) for at least 6 months, were enrolled in a prospective cross-sectional study. All patients underwent Dynamic Power Doppler after intracavernous injection of vasoactive drugs (PGE1 20 mcg and Papaverine 6 mg). Poor responders' patients subsequently underwent to cavernosometry to get a full assessment of the vascular framework.
RESULTS
202 patients (mean age 46 years), were included in the study. 96 subjects (47.5%) who did not adequately respond to the intracavernous injection -test, subsequently underwent to cavernosometry. In 42 of 96 patients (43.7%) cavernosometry was positive for veno-occlusive dysfunction. In a total of 160 patients who did not have veno-occlusive dysfunction (54 with negative cavernosometry + 106 intracavernous injection-test responders), the Power Doppler was normal in 126 (78.8%) and pathological in 34 (21.3%) in terms of steric conformation of "low flow" vessels corresponding to the Cavernosal Terminal Unit. The diagnostic sensitivity of Power Doppler towards veno-occlusive dysfunction was found to be 52.4% (Positive Predictive Value: 39.3%), the specificity was 78.8% (Negative Predictive Value: 86.3%) and the total diagnostic accuracy was equal to 73.3%.
CONCLUSION
Collected data evidenced that patients who reported altered morphological features of the Cavernosal Terminal Unit had an approximately 4-fold greater risk of having veno-occlusive dysfunction compared to patients who had normal Power Doppler features (OR = 4.076; 95% CI: 1.996-8.327).
Topics: Male; Humans; Middle Aged; Erectile Dysfunction; Cross-Sectional Studies; Prospective Studies; Penis; Ultrasonography
PubMed: 35988732
DOI: 10.1016/j.urology.2022.08.009 -
Cellular and Molecular Biology... Mar 2022This work was to investigate TiO2 nanocrystalline film material in heart valve replacement (HVR) and the effect of papaverine infusion through the aortic root before...
This work was to investigate TiO2 nanocrystalline film material in heart valve replacement (HVR) and the effect of papaverine infusion through the aortic root before cardiac self-recovery during the HVR. TiO2 nanocrystalline films were prepared by radio frequency (RF) reactive sputtering. The crystallization characteristics and surface morphology of TiO2 nanocrystalline films were observed by X-ray diffraction and scanning electron microscopy, and the anti-platelet adhesion and anti-coagulation properties of the films were analyzed. 86 patients with heart valve disease were selected and all underwent HVR. They were randomly divided into a control group (routine treatment) and an experimental group (papaverine perfusion through aortic root), with 43 cases in each group. The rate of cardiac self-recovery and the dosage of dopamine were observed. The results showed that the TiO2 nanocrystalline film was composed of a large number of uniform particles, and the average particle size was about 18.97 ± 7.28 nm. The rate of cardiac self-recovery in the experimental group was 97.67%, which was significantly higher than that in the control group (67.44%) (P< 0.05). The dosage of epinephrine, dopamine, and duration of cardiopulmonary bypass (CPB) assistance in the observation group were less than those in the control group (P < 0.05). These results indicated that TiO2 nanocrystalline film could be used in HVR, and papaverine infusion through aortic root before HVR and myocardial protection measures can significantly improve the rate of cardiac self-recovery and promote postoperative recovery.
Topics: Dopamine; Heart Valves; Humans; Papaverine; Titanium
PubMed: 35988206
DOI: 10.14715/cmb/2022.68.3.35 -
Proceedings of the National Academy of... Aug 2022Tetrahydropapaverine (THP) and papaverine are plant natural products with clinically significant roles. THP is a precursor in the production of the drugs atracurium and...
Tetrahydropapaverine (THP) and papaverine are plant natural products with clinically significant roles. THP is a precursor in the production of the drugs atracurium and cisatracurium, and papaverine is used as an antispasmodic during vascular surgery. In recent years, metabolic engineering advances have enabled the production of natural products through heterologous expression of pathway enzymes in yeast. Heterologous biosynthesis of THP and papaverine could play a role in ensuring a stable supply of these clinically significant products. Biosynthesis of THP and papaverine has not been achieved to date, in part because multiple pathway enzymes have not been elucidated. Here, we describe the development of an engineered yeast strain for de novo biosynthesis of THP. The production of THP is achieved through heterologous expression of two enzyme variants with activity on nonnative substrates. Through protein engineering, we developed a variant of -methylcoclaurine hydroxylase with activity on coclaurine, enabling de novo norreticuline biosynthesis. Similarly, we developed a variant of scoulerine 9--methyltransferase capable of -methylating 1-benzylisoquinoline alkaloids at the 3' position, enabling de novo THP biosynthesis. Flux through the heterologous pathway was improved by knocking out yeast multidrug resistance transporters and optimization of media conditions. Overall, strain engineering increased the concentration of biosynthesized THP 600-fold to 121 µg/L. Finally, we demonstrate a strategy for papaverine semisynthesis using hydrogen peroxide as an oxidizing agent. Through optimizing pH, temperature, reaction time, and oxidizing agent concentration, we demonstrated the ability to produce semisynthesized papaverine through oxidation of biosynthesized THP.
Topics: Biological Products; Cytochrome P-450 Enzyme System; Hydrogen Peroxide; Oxidants; Papaverine; Plant Proteins; Protein Engineering; Saccharomyces cerevisiae
PubMed: 35939674
DOI: 10.1073/pnas.2205848119 -
Clinical, Cosmetic and Investigational... 2022Blindness caused by embolization of fillers is a rare but catastrophic complication after cosmetic injection. Vision improvement is rarely reported among the various...
Blindness caused by embolization of fillers is a rare but catastrophic complication after cosmetic injection. Vision improvement is rarely reported among the various studies on potential clinical treatments. In this case, the patient suffered from ophthalmic artery occlusion with no light perception 48 h after hyaluronic acid injection. After two intra-arterial thrombolytic therapy sessions and traditional sequential therapy, ocular appearance was restored to normal, blood supply to the retina and visual function were improved, and visual acuity was restored to hand motion levels. Our results suggest that intra-arterial thrombolytic therapy with hyaluronidase and papaverine has a positive effect on hyaluronic acid-induced visual loss and is worthy of clinical promotion.
PubMed: 35935598
DOI: 10.2147/CCID.S367481 -
Foods (Basel, Switzerland) Jul 2022In this work, the thermal degradation of tropane and opium alkaloids was studied in samples of breadsticks prepared with corn flour, contaminated with seeds of , and...
Evaluation of Thermal Degradation of Tropane and Opium Alkaloids in Gluten-Free Corn Breadsticks Samples Contaminated with Stramonium Seeds and Baked with Poppy Seeds under Different Conditions.
In this work, the thermal degradation of tropane and opium alkaloids was studied in samples of breadsticks prepared with corn flour, contaminated with seeds of , and containing seeds of L. A total of seven different samples were prepared and eight alkaloids were studied, three tropane (atropine, scopolamine, and anisodamine) and five opium (morphine, codeine, thebaine, papaverine, and noscapine) alkaloids. For this purpose, a fast, easy and efficient method based on solid-liquid extraction (SLE) prior to the analysis by high-performance liquid chromatography with a diode array detector (HPLC-DAD) was developed and validated. Thermal degradation studies showed a decrease in the TAs and OAs content under baking (180 °C for 20 min) that was between 7-65% for atropine, depending on the preparation conditions used, between 35-49% for scopolamine and anisodamine, up to 100% for morphine and codeine and between 14-58% for thebaine, papaverine, and noscapine. Results also evidenced that degradation of morphine and codeine was higher when the seeds were added as topping to the breadsticks.
PubMed: 35892780
DOI: 10.3390/foods11152196 -
Toxins Jul 2022Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As...
Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As bleeding was suggested to be a side effect of the isoquinoline alkaloid berberine, we decided to ascertain if different isoquinoline alkaloids could influence hemocoagulation through the inhibition of either platelet aggregation or blood coagulation. Initially, a total of 14 compounds were screened for antiplatelet activity in whole human blood by impedance aggregometry. Eight of them demonstrated an antiplatelet effect against arachidonic acid-induced aggregation. Papaverine and bulbocapnine were the most potent compounds with biologically relevant IC values of 26.9 ± 12.2 μM and 30.7 ± 5.4 μM, respectively. Further testing with the same approach confirmed their antiplatelet effects by employing the most physiologically relevant inducer of platelet aggregation, collagen, and demonstrated that bulbocapnine acted at the level of thromboxane receptors. None of the alkaloids tested had an effect on blood coagulation measured by a mechanical coagulometer. In conclusion, the observed antiplatelet effects of isoquinoline alkaloids were found mostly at quite high concentrations, which means that their clinical impact is most likely low. Bulbocapnine was an exception. It proved to be a promising antiplatelet molecule, which may have biologically relevant effects.
Topics: Alkaloids; Blood Platelets; Humans; Isoquinolines; Platelet Aggregation; Platelet Aggregation Inhibitors
PubMed: 35878229
DOI: 10.3390/toxins14070491 -
Frontiers in Pharmacology 2022Erectile dysfunction is increasingly affecting men, from the elderly to young adults, being a sexual disorder related to the inability to generate or maintain a penile... (Review)
Review
Erectile dysfunction is increasingly affecting men, from the elderly to young adults, being a sexual disorder related to the inability to generate or maintain a penile erection. This disorder is related to psychosocial factors such as anxiety, depression, and low self-esteem, to organic factors such as the presence of preexisting conditions like hypertension, diabetes and dyslipidemia. The pathophysiology of the disease is related to changes in the neurotransmission of the autonomic or the non-cholinergic non-adrenergic nervous system, as well as the release of local mediators, such as thromboxane A and endothelin, and hormonal action. These changes lead to impaired relaxation of cavernous smooth muscle, which reduces local blood flow and impairs penile erection. Currently, therapy is based on oral vasodilation, such as sildenafil, tadalafil, vardenafil and iodenafil, or by direct administration of these agents into the corpus cavernosum or by intraurethral route, such as alprostadil and papaverine. Despite this, studies that consolidate the understanding of its pathophysiological process contribute to the discovery of new more efficient drugs for the treatment of erectile dysfunction. In this sense, in the present work an extensive survey was carried out of the mechanisms already consolidated and the most recent ones related to the development of erectile dysfunction.
PubMed: 35865945
DOI: 10.3389/fphar.2022.895044