Investigation of carbonic anhydrase inhibitory effects and cytotoxicities of pyrazole-based hybrids carrying hydrazone and zinc-binding benzenesulfonamide pharmacophores.

Pyrazole-based carbohydrazone hybrids have been considered to be a remarkable class of compounds in pharmaceutical chemistry. Here, we reported bioactivities of 4-(3-(2-(arylidene)hydrazin-1-carbonyl)-5-phenyl-1H-pyrazol-1-yl)benzenesulfonamides (1-27) towards CA isoenzymes (hCA I, hCA II, hCA IX) and human oral squamous cell carcinoma cell line. Compounds 19 (Ki = 10.1 nM, hCA I/hCA IX = 749.6), 22 (Ki = 18.5 nM, hCA I/hCA IX = 429.2), 26 (Ki = 14.5 nM, hCA I/hCA IX = 596.9), 27 (Ki = 21.5 nM, hCA I/hCA IX = 413.1) were more potent and selective inhibitors of cancer-associated hCA IX isoenzyme. Compounds 22 and 26 were also found to be approximately three times more selective hCA IX inhibitors over off-target hCA II at low nanomolar. Compounds 19, 22, 23, 24, and 26 with IC50 of 1.6-1.7 µM showed potent cytotoxicity against human oral squamous cell carcinoma cell line as compared with human gingival fibroblast, producing the tumor-specificity value over 100. This was due to its cytostatic growth inhibition accompanied by a slight but significant dose-dependent increase in cell shrinkage and subG1 cell accumulation and marginal activation of caspase 3 substrates. Bioassay results showed that carbohydrazone-based hybrids could be useful candidates to design novel anticancer compounds and selective carbonic anhydrase inhibitors.

Orthodontic treatment-induced temporal alteration of jaw-opening reflex excitability.

The impairment of orofacial motor function during orthodontic treatment needs to be addressed, because most orthodontic patients experience pain and motor excitability would be affected by pain. In the present study, the temporal alteration of the jaw-opening reflex excitability was investigated to determine if orthodontic treatment affects orofacial motor function. The excitability of jaw-opening reflex evoked by electrical stimulation on the gingiva and recorded bilaterally in the anterior digastric muscles was evaluated at 1 (D1), 3 (D3), and 7 days (D7) after orthodontic force application to the teeth of right side; morphological features (e.g., osteoclast genesis and tooth movement) were also evaluated. To clarify the underlying mechanism of orthodontic treatment-induced alteration of orofacial motor excitability, analgesics were administrated for 1 day. At D1 and D3, orthodontic treatment significantly decreased the threshold for inducing the jaw-opening reflex but significantly increased the threshold at D7. Other parameters of the jaw-opening reflex were also evaluated (e.g., latency, duration and area under the curve of anterior digastric muscles activity), and only the latency of the D1 group was significantly different from that of the other groups. Temporal alteration of the jaw-opening reflex excitability was significantly correlated with changes in morphological features. Aspirin (300 mg·kg-1·day-1) significantly increased the threshold for inducing the jaw-opening reflex, whereas a lower dose (75-150 mg·kg-1·day-1) of aspirin or acetaminophen (300 mg·kg-1·day-1) failed to alter the jaw-opening reflex excitability. These results suggest that an increase of the jaw-opening reflex excitability can be induced acutely by orthodontic treatment, possibly through the cyclooxygenase activation.NEW & NOTEWORTHY It is well known that motor function is affected by pain, but the effect of orthodontic treatment-related pain on the trigeminal motor excitability has not been fully understood. We found that, during orthodontic treatment, trigeminal motor excitability is acutely increased and then decreased in a week. Because alteration of trigeminal motor function can be evaluated quantitatively by jaw-opening reflex excitability, the present animal model may be useful to search for alternative approaches to attenuate orthodontic pain.

Synthesis of some acrylophenones with N-methylpiperazine and evaluation of their cytotoxicities.

In this study, the compounds having acrylophenone structure, 1-aryl-2-(N-methylpiperazinomethyl)-2-propen-1-one dihydrochlorides, were synthesized and their chemical structures were identified with (1)H NMR, (13)C NMR and HRMS spectra. The cytotoxicities of the compounds were tested towards Ca9-22 (human gingival carcinoma), HSC-2 (human oral squamous carcinoma), HSC-3 (human oral squamous carcinoma) and HSC-4 (human oral squamous carcinoma) cell lines as tumor cell lines and HGF (gingival fibroblasts), HPLF (periodontal ligament fibroblasts) and HPC (pulp cells) cell lines as non-tumor cell lines. PSE of the compound TA2, which has a methyl substituent on phenyl ring, pointed out the compound TA2 as a leader compound to be considered.

Synthesis of mono Mannich bases of 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1-one and evaluation of their cytotoxicities.

Chalcones and Mannich bases are a group of compounds known for their cytotoxicities. In this study restricted chalcone analogue, compound 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1-one MT1, was used as a starting compound to synthesize new mono Mannich bases since Mannich bases may induce more cytotoxicity than chalcone analogue that they are derived from by producing additional alkylating center for cellular thiols. In this study, cyclic and acyclic amines were used to synthesize Mannich bases. All compounds were tested against Ca9-22 (gingival carcinoma), HSC-2, HSC-3 and HSC-4 (oral squamous cell carcinoma) as tumour cell lines and HGF (gingival fibroblasts), HPC (pulp cells) and HPLF (periodontal ligament fibroblasts) human normal oral cells as non tumour cell lines. Cytotoxicity, selectivity index (SI) values and potency selectivity expression (PSE) values expressed as a percentage were determined for the compounds. According to data obtained, the compound MT8 with the highest PSE value bearing N-methylpiperazine moiety seems to be a good candidate to develop new cytotoxic compounds and is suited for further investigation.

Synthesis and bioactivity studies of 1-aryl-3-(2-hydroxyethylthio)-1-propanones.

A series of Mannich bases having piperidine moiety were reacted with 2-mercaptoethanol, leading to 1-aryl-3-piperidine-4-yl-1-propanone hydrochlorides. The cytotoxicity and carbonic anhydrase inhibitory activities of these new compounds were evaluated. Among the compounds, only one derivative, nitro substituent bearing EU9, showed an effective cytotoxicity, although weak tumor specificity against human oral malignant versus nonmalignant cells. The compound induced apoptosis in HSC-2 oral squamous cell carcinoma cells, but not in human gingival fibroblast. Chemical modifications of this lead are thus necessary to further investigate it as a drug candidate and to obtain compounds with a better activity profile.

Synthesis, cytotoxicity and carbonic anhydrase inhibitory activities of new pyrazolines.

A series of polymethoxylated-pyrazoline benzene sulfonamides were synthesized, investigated for their cytotoxic activities on tumor and non-tumor cell lines and inhibitory effects on carbonic anhydrase isoenzymes (hCA I and hCA II). Although tumor selectivity (TS) of the compounds were less than the reference compounds 5-Fluorouracil and Melphalan, trimethoxy derivatives 4, 5, and 6 were more selective than dimethoxy derivatives 2 and 3 as judged by the cytotoxicity assay with the cells both types originated from the gingival tissue. The compound 6 (4-[3-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl] benzene sulfonamide) showed the highest TS values and can be considered as a lead molecule of the series for further investigations. All compounds synthesized showed superior CA inhibitory activity than the reference compound acetazolamide on hCA I, and II isoenzymes, with inhibition constants in the range of 26.5-55.5 nM against hCA I and of 18.9-28.8 nM against hCA II, respectively.

Biological activities and possible dental application of three major groups of polyphenols.

The present article reviewed the biological activities and possible dental application of three major polyphenols, i.e., lignin-carbohydrate complexes, tannins, and flavonoids, citing mostly our in vitro studies together with those from other groups. All these polyphenols showed much lower tumor-selective cytotoxicity against oral squamous cell carcinoma cells vs. normal oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast), in comparison to popular chemotherapeutic antitumor drugs. Several compounds showing higher tumor-selectivity did not induce internucleosomal DNA fragmentation, a biochemical hallmark of apoptosis, in oral carcinoma cell lines. Lignin-carbohydrate complex protected the cells from the cytopathic effects of HIV infection and UV irradiation more efficiently than other polyphenols. Limited digestion of lignin-carbohydrate complex suggests that the lignin moiety is involved in the prominent anti-HIV activity, whereas the carbohydrate moiety may function in immunopotentiating activity through a cell surface receptor. Alkaline extract of plant leaf, which contains higher amounts of lignin-carbohydrate complex, showed potent anti-inflammatory action against IL-1ß-stimulated human gingival fibroblasts. Local application of lignin-carbohydrate complex through oral mucosa is recommended, considering its poor intestinal absorption.

Augmentation of Therapeutic Efficacy of Extraction of Causative Teeth by Irrigation for Odontogenic Maxillary Sinusitis.

BACKGROUND/AIM: Odontogenic maxillary sinusitis is a clinically popular disease, but radical surgery and endoscopic surgery are often required. In the present study, we compared for the first time the therapeutic efficacy of the extraction of causative teeth with or without irrigation of the extraction fossa. PATIENTS AND METHODS: A total of 60 patients underwent extraction of causative tooth. Among them, 34 patients underwent irrigation, while other 26 patients did not. Based on computed tomography (CT) images, treatment efficacy was quantified by the percentage of the remaining maxillary sinus mucosal lesions. The extent of therapeutic efficacy was evaluated following five grades, based on the percentage of remaining lesions: Grade 1 (0%) (disappearance of lesions), Grade 2 (roughly 10%), Grade 3 (roughly 30%), Grade 4 (approximately 50%) and Grade 5 (100%) (no improvement of the lesions). RESULTS: Irrigation significantly augmented the therapeutic efficacy of tooth extraction for maxillary sinus mucosal lesions (mean grade: decreasing from 3.27 to 1.35). CONCLUSION: The combination of tooth extraction and irrigation may contribute to the reduction of the necessity of surgery for the maxillary sinuses.

Photodynamic Therapy With Resveratrol and an Nd:YAG Laser for Enterococcus faecalis Elimination.

BACKGROUND/AIM: Enterococcus faecalis is the leading cause of endodontic treatment failures. Despite various conventional disinfection approaches, microorganisms often persist in root canals. Photodynamic therapy (PDT) is an adjunct antimicrobial strategy employing a nontoxic photosensitizer (PS) and light source. This study evaluated the antimicrobial effect of PDT using an Nd:YAG laser and resveratrol (RSV) with or without pigment, and confirmed that RSV is nontoxic as a PS. MATERIALS AND METHODS: We employed laser irradiation at a 3W output power, using RSV and red pigment as the PS, on an E. faecalis bacterial solution. Subsequently, colony-forming units were quantified. The impact of RSV on osteoblasts was measured using an MTT assay. RESULTS: E. faecalis counts declined after laser irradiation. The combined application of laser irradiation with RSV, red pigment, or both showed a reduction compared to no irradiation and control groups without RSV and red pigment. The 50% cytotoxic concentration against osteoblast cells from mice incubated with RSV for 48 h was 162 µM. The value with RSV and laser was 201 µM and that with RSV and red pigment was 199 µM. The value with RSV, laser and red pigment was 357 µM. CONCLUSION: The combination of Nd:YAG laser irradiation and RSV as the PS with pigment was efficacious for E. faecalis elimination without inducing any toxic effects on osteoblasts. This combination holds potential as a root canal irrigation strategy.

Dectin-1/SYK Activation Induces Antimicrobial Peptide and Negative Regulator of NF-κB Signaling in Human Oral Epithelial Cells.

BACKGROUND/AIM: Oral epithelial cells serve as the primary defense against microbial exposure in the oral cavity, including the fungus Candida albicans. Dectin-1 is crucial for recognition of ß-glucan in fungi. However, expression and function of Dectin-1 in oral epithelial cells remain unclear. MATERIALS AND METHODS: We assessed Dectin-1 expression in Ca9-22 (gingiva), HSC-2 (mouth), HSC-3 (tongue), and HSC-4 (tongue) human oral epithelial cells using flow cytometry and real-time polymerase chain reaction. Cell treated with ß-glucan-rich zymosan were evaluated using real-time polymerase chain reaction. Phosphorylation of spleen-associated tyrosine kinase (SYK) was analyzed by western blotting. RESULTS: Dectin-1 was expressed in all four cell types, with high expression in Ca9-22 and HSC-2. In Ca9-22 cells, exposure to ß-glucan-rich zymosan did not alter the mRNA expression of chemokines nor of interleukin (IL)6, IL8, IL1ß, IL17A, and IL17F. Zymosan induced the expression of antimicrobial peptides ß-defensin-1 and LL-37, but not S100 calcium-binding protein A8 (S100A8) and S100A9. Furthermore, the expression of cylindromatosis (CYLD), a negative regulator of nuclear factor kappa B (NF-κB) signaling, was induced. In HSC-2 cells, zymosan induced the expression of IL17A. The expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), a negative regulator of NF-κB signaling, was also induced. Expression of other cytokines and antimicrobial peptides remained unchanged. Zymosan induced phosphorylation of SYK in Ca9-22 cells, as well as NF-κB. CONCLUSION: Oral epithelial cells express Dectin-1 and recognize ß-glucan, which activates SYK and induces the expression of antimicrobial peptides and negative regulators of NF-κB, potentially maintaining oral homeostasis.

Efficacy of toothpaste containing Brazilian green propolis extracts with an optimal kaempferide/betuletol ratio for improving oral microbiota: A randomized, controlled, paired crossover study.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a resinous substance collected by honeybees from various plant sources and has been used in traditional folk medicine for centuries. Propolis has various biological properties, including antibacterial, antiviral, anti-inflammatory, and anti-tumor properties. The use of propolis in oral health care is attributable to its antimicrobial and anti-inflammatory effects. However, limited evidence exists on the in vivo efficacy of propolis against periodontal pathogens. AIM OF THE STUDY: We aimed to evaluate the efficacy of Brazilian green propolis (BGP)-containing toothpaste for improving the oral environment and define its antibacterial compounds. MATERIALS AND METHODS: Overall, 48 student volunteers aged 18-40 years (24 females and 24 males) were randomly categorized into the BGP and placebo groups. The BGP and placebo groups received toothpaste with and without BGP, respectively. After a baseline assessment, the plaque index (PI) score, gingival index (GI) score, and proportion of periodontal pathogens on the tongue surface were analyzed at 0, 1, and 2 weeks. Antibacterial compounds were identified using liquid-liquid partitioning, high-performance liquid chromatography purification, and nuclear magnetic resonance methods. RESULTS: The concentration of BGP in the toothpaste was set at 0.0347 w/v%. Compared with the placebo group, the BGP group demonstrated a reduction in the PI score (p<0.05) but not in the GI score, as well as a reduction in Porphyromonas gingivalis (Pg)/Total bacteria (Tb), Fusobacterium nucleatum (Fn)/Tb, and Aggregatibacter actinomycetemcomitans (Aa)/Tb (p<0.05) but not in Streptococcus salivalius/Tb. Effect sizes for Pg, Fn and Aa were 0.360, 0.556, and 0.164, respectively. The antibacterial compounds of the BGP-containing toothpaste included a mixture of kaempferide/betuletol. CONCLUSIONS: We confirmed the efficacy of propolis toothpaste with an optimal kaempferide/betuletol ratio for improving oral microbiota, thereby suggesting that BGP toothpaste is clinically useful in maintaining oral health and preventing periodontal disease.

Dimeric 3,5-Bis(benzylidene)-4-piperidones: Tumor-Selective Cytotoxicity and Structure-Activity Relationships.

Background: The objective of this study is to find novel antineoplastic agents that display greater toxicity to malignant cells than to neoplasms. In addition, the mechanisms of action of representative compounds are sought. This report describes the cytotoxicity of a number of dimers of 3,5-bis(benzylidene)-4-piperidones against human malignant cells (promyelocytic leukemia HL-60 and squamous cell carcinoma HSC-2, HSC-3, and HSC-4). Methods: Tumor specificity was evaluated by the selectivity index (SI), that is the ratio of the mean CC50 for human non-malignant oral cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) to that for malignant cells. Results: The compounds were highly toxic to human malignant cells. On the other hand, these molecules were less toxic to human non-malignant cells. In particular, a potent lead molecule, 3b, was identified. A QSAR study revealed that the placement of electron-releasing and hydrophilic substituents into the aryl rings led to increases in cytotoxic potencies. The modes of action of a lead compound discovered in this study designated 3b were the activation of caspases-3 and -7, as well as causing PARP1 cleavage and G2 arrest, followed by sub-G1 accumulation in the cell cycle. This compound also depolarized the mitochondrial membrane and generated reactive oxygen species in human colon carcinoma HCT116 cells. In conclusion, this study has revealed that, in general, the compounds described in this report are tumor-selective cytotoxins.

In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations.

Oral cancer is a severe health problem that accounts for an alarmingly high number of fatalities worldwide. Withania somnifera (L.) Dunal has been extensively studied against various tumor cell lines from different body organs, rarely from the oral cavity. We thus investigated the cytotoxicity of W. somnifera fruits (W-F) and roots (W-R) hydromethanolic extracts and their chromatographic fractions against oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingiva), HSC-2, HSC-3, and HSC-4 (derived from tongue)] and three normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF), and human pulp cells (HPC)] in comparison to standard drugs. The root polar ethyl acetate (W-R EtOAc) and butanol (W-R BuOH) fractions exhibited the strongest cytotoxicity against the Ca9-22 cell line (CC50 = 51.8 and 40.1 µg/mL, respectively), which is relatively the same effect as 5-FU at CC50 = 69.4 µM and melphalan at CC50 = 36.3 µM on the same cancer cell line. Flow cytometric analysis revealed changes in morphology as well as in the cell cycle profile of the W-R EtOAc and W-R BuOH-treated oral cancer Ca9-22 cells compared to the untreated control. The W-R EtOAc (125 µg/mL) exerted morphological changes and induced subG1 accumulation, suggesting apoptotic cell death. A UHPLC MS/MS analysis of the extract enabled the identification of 26 compounds, mainly alkaloids, withanolides, withanosides, and flavonoids. Pharmacophore-based inverse virtual screening proposed that BRD3 and CDK2 are the cancer-relevant targets for the annotated withanolides D (18) and O (12), and the flavonoid kaempferol (11). Molecular modeling studies highlighted the BRD3 and CDK2 as the most probable oncogenic targets of anticancer activity of these molecules. These findings highlight W. somnifera's potential as an affordable source of therapeutic agents for a range of oral malignancies.

1-(3-aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones: a novel group of tumour-selective cytotoxins.

Two series of 1-(3-aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones, designed as novel cytotoxins, were synthesized. The compounds had low CC50 values in the micromolar range against HL-60 promyelocytic leukemic cells and HSC-2, HSC-3 and HSC-4 oral squamous cell carcinomas. The CC50 values of these compounds were higher towards non-malignant HGF (gingival fibroblasts), HPC (pulp cells), and HPLF (periodontal ligament fibroblasts) cells, which reveals the tumour-selectivity of these enones. A representative compound 4c caused cleavage of PARP1 in HSC-2 cells but not in HGF cells, which may be a contributing factor to the tumour-selectivity.

Cytotoxicity, Differentiation, and Biocompatibility of Root-End Filling: A Comprehensive Study.

Assessing the biocompatibility of endodontic root-end filling materials through cell line responses is both essential and of utmost importance. This study aimed to the cytotoxicity of the type of cell death through apoptosis and autophagy, and odontoblast cell-like differentiation effects of MTA, zinc oxide-eugenol, and two experimental Portland cements modified with bismuth (Portland Bi) and barium (Portland Ba) on primary cell cultures. Material and methods: The cells corresponded to human periodontal ligament and gingival fibroblasts (HPLF, HGF), human pulp cells (HPC), and human squamous carcinoma cells from three different patients (HSC-2, -3, -4). The cements were inoculcated in different concentrations for cytotoxicity evaluation, DNA fragmentation in electrophoresis, apoptosis caspase activation, and autophagy antigen reaction, odontoblast-like cells were differentiated and tested for mineral deposition. The data were subject to a non-parametric test. Results: All cements caused a dose-dependent reduction in cell viability. Contact with zinc oxide-eugenol induced neither DNA fragmentation nor apoptotic caspase-3 activation and autophagy inhibitors (3-methyladenine, bafilomycin). Portland Bi accelerated significantly (p < 0.05) the differentiation of odontoblast-like cells. Within the limitation of this study, it was concluded that Portland cement with bismuth exhibits cytocompatibility and promotes odontoblast-like cell differentiation. This research contributes valuable insights into biocompatibility, suggesting its potential use in endodontic repair and biomimetic remineralization.

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs.

Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds in comparison with four popular anti-cancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one order of magnitude higher TSM than newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two orders of magnitude lower TSE than Compounds A and B. Compounds A and B showed higher TSM, TSE, and TSN values than doxorubicin, 5-FU, and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that Compounds A and B may inhibit the signaling pathway of estrogen-related receptors.

Disruption of programmed masticatory movements in unilateral MPTP-treated monkeys as a model of jaw movement abnormality in Parkinson's disease.

While motor disturbance in Parkinson's disease can affect innate, programmed processes, such as masticatory mandibular movements, the pathophysiology of such abnormalities remains unclear. This study applies digital analysis by high-speed video signal processing that tracks three dots placed around the mouth for recording masticatory movements in unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. The system analyzes displacement, velocity and cycle duration of the topography of mandibular movement during mastication of sweet potato slices. In monkeys receiving MPTP into the right carotid artery (n = 3), positron emission tomography indicated significant reduction in the binding of (E)-N-(3-iodoprop-2-enyl)-2ß-carbo[(11)C]methoxy-3ß-(4-methylphenyl)nortropane ([(11)C]PE2I) to the dopamine transporter in the right caudate, putamen, nucleus accumbens and substantia nigra relative to the contralateral hemisphere. These monkeys showed hypokinesia of the left forelimbs and hindlimbs. During mastication, MPTP-treated monkeys chewed preferentially on the left side, while untreated monkeys (n = 3) showed no preference for chewing side. The amplitude of vertical opening and closing movements was reduced in MPTP-treated monkeys, with a slight but significant increase in the lateral component of mandibular movements. The velocity of all phases of horizontal mandibular movements was reduced. In consequence, duration of the occlusal phase was increased, while duration of the closing phase was decreased in MPTP-treated monkeys. These findings indicate that during masticatory movements MPTP-treated monkeys chew preferentially on the side contralateral to loss of dopamine neurons, with reduced amplitude and velocity of mandibular movements. High-speed digital movement analysis is able to define and quantify abnormalities of orofacial movement topography as a sign of parkinsonism.

Prominent Anti-UVC Activity of Lignin Degradation Products.

BACKGROUND/AIM: The rapid spread of COVID-19 resulted in the revision of the value of ultraviolet C (UVC) sterilization in working spaces. This study aimed at re-evaluating the anti-UVC activity of four groups of natural products against human melanoma COLO679 and human normal dermal fibroblast (HDFa) cells, based on chemotherapeutic index. MATERIALS AND METHODS: Various cell lines were exposed to UVC for 3 min in the presence of increasing concentrations of test compounds and viable cell numbers were determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The anti-UVC activity was quantified by the ratio of the 50% cytotoxic concentration (determined without irradiation) to the 50% effective concentration (which abolished by 50% the UVC-induced loss of viability). Apoptosis was quantified as the subG1 population proportion following cell-cycle analysis. RESULTS: Among four groups of major natural products, six phenylpropanoids showed the highest anti-UVC activity, followed by the lignified products and alkaline products that contain lignin and its degradation products. On the other hand, tannins and flavonoids showed lower activity due to their higher cytotoxicity. UVC-sensitive COLO679 cells lack dectin-1 protein expression. CONCLUSION: These data suggest the prominent anti-UVC activity of lignin degradation products, and the possible involvement of dectin-1 expression in UVC-sensitivity.

Effect of Underwater Exercise on Salivary Metabolites of Older Persons With Disability.

BACKGROUND/AIM: Underwater exercise is aimed at preventing aging, maintaining, and improving motor function, and improving physical function. However, its rehabilitation effects have not been well evaluated. In order to gain insight into the molecular basis of its rehabilitation effects, possible changes in the salivary metabolites of four older persons with disability (mean age: 72.5 years) during underwater exercise were investigated. MATERIALS AND METHODS: Halitosis was measured by Breathtron; salivary bacterial number by bacterial counter; amino acids by amino acid analyzer; 8-oxoguanine by ELISA; and intracellular metabolites by capillary electrophoresis, time-of-flight mass spectrometry, liquid chromatography, and triode quadrupole mass spectrometry. RESULTS: Underwater exercise induced apparent declines in two major salivary amino acids (glycine and proline) and bacterial numbers in the cheek mucosa and salivary, without apparent changes in the halitosis and urine 8-oxoguanine concentration. Older subjects showed higher concentrations of most of 166 metabolites compared to young volunteers (mean age: 38.8 years old). Fifteen compounds were significantly reduced with the progression of underwater exercise. CONCLUSION: Improvement of upright balance function with underwater exercise is correlated with several salivary components.

Steroidal constituents isolated from the seeds of Withania somnifera.

A new withanolide glycoside (1), two new ergostanol glycosides (2 and 3), and a new furostanol glycoside (4), along with nine known steroidal derivatives (5-12) were isolated from the seeds of Withania somnifera. The structures of the new compounds were determined using spectroscopic analysis and hydrolysis. The cytotoxic activities of the isolated compounds were evaluated against Ca9-22 human gingival carcinoma cells, HSC-2 human mouth carcinoma cells, and HL-60 human promyelocytic leukemia cells. Only 12 exhibited cytotoxic activity against these cell lines with IC50 values of 0.38, 0.54, and 1.5 µM, respectively.