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1.
FASEB J ; 34(4): 4870-4889, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32077151

RESUMO

The COP9 signalosome (CSN) is a conserved eukaryotic complex, essential for vitality in all multicellular organisms and critical for the turnover of key cellular proteins through catalytic and non-catalytic activities. Saccharomyces cerevisiae is a powerful model organism for studying fundamental aspects of the CSN complex, since it includes a conserved enzymatic core but lacks non-catalytic activities, probably explaining its non-essentiality for life. A previous transcriptomic analysis of an S. cerevisiae strain deleted in the CSN5/RRI1 gene, encoding to the CSN catalytic subunit, revealed a downregulation of genes involved in lipid metabolism. We now show that the S. cerevisiae CSN holocomplex is essential for cellular lipid homeostasis. Defects in CSN assembly or activity lead to decreased quantities of ergosterol and unsaturated fatty acids (UFA); vacuole defects; diminished lipid droplets (LDs) size; and to accumulation of endoplasmic reticulum (ER) stress. The molecular mechanism behind these findings depends on CSN involvement in upregulating mRNA expression of SPT23. Spt23 is a novel activator of lipid desaturation and ergosterol biosynthesis. Our data reveal for the first time a functional link between the CSN holocomplex and Spt23. Moreover, CSN-dependent upregulation of SPT23 transcription is necessary for the fine-tuning of lipid homeostasis and for cellular health.


Assuntos
Complexo do Signalossomo COP9/metabolismo , Ergosterol/biossíntese , Ácidos Graxos Insaturados/metabolismo , Proteínas de Membrana/metabolismo , Metaloendopeptidases/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , Complexo do Signalossomo COP9/genética , Estresse do Retículo Endoplasmático , Ergosterol/genética , Ácidos Graxos Insaturados/genética , Deleção de Genes , Gotículas Lipídicas/metabolismo , Proteínas de Membrana/genética , Metaloendopeptidases/genética , Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética
2.
Int J Mol Sci ; 22(2)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33418880

RESUMO

Transforming growth factor ß (TGFß) is a secreted growth and differentiation factor that influences vital cellular processes like proliferation, adhesion, motility, and apoptosis. Regulation of the TGFß signaling pathway is of key importance to maintain tissue homeostasis. Perturbation of this signaling pathway has been implicated in a plethora of diseases, including cancer. The effect of TGFß is dependent on cellular context, and TGFß can perform both anti- and pro-oncogenic roles. TGFß acts by binding to specific cell surface TGFß type I and type II transmembrane receptors that are endowed with serine/threonine kinase activity. Upon ligand-induced receptor phosphorylation, SMAD proteins and other intracellular effectors become activated and mediate biological responses. The levels, localization, and function of TGFß signaling mediators, regulators, and effectors are highly dynamic and regulated by a myriad of post-translational modifications. One such crucial modification is ubiquitination. The ubiquitin modification is also a mechanism by which crosstalk with other signaling pathways is achieved. Crucial effector components of the ubiquitination cascade include the very diverse family of E3 ubiquitin ligases. This review summarizes the diverse roles of E3 ligases that act on TGFß receptor and intracellular signaling components. E3 ligases regulate TGFß signaling both positively and negatively by regulating degradation of receptors and various signaling intermediates. We also highlight the function of E3 ligases in connection with TGFß's dual role during tumorigenesis. We conclude with a perspective on the emerging possibility of defining E3 ligases as drug targets and how they may be used to selectively target TGFß-induced pro-oncogenic responses.


Assuntos
Neoplasias/patologia , Fator de Crescimento Transformador beta/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Transição Epitelial-Mesenquimal , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Neovascularização Patológica , Transdução de Sinais , Proteínas Smad/metabolismo , Ubiquitinação
3.
J Contemp Dent Pract ; 22(7): 763-768, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34615781

RESUMO

AIM AND OBJECTIVE: To carry out comparison of apical root resorption (ARR) in the fixed orthodontic appliance and clear aligners with the help of cone-beam computed tomography (CBCT) imaging. METHODS AND MATERIALS: The study was conducted on 576 roots in 110 patients. These patients were divided into two groups such that each group consisted of 55 patients. A total of 288 roots were analyzed in each group. One group consisted of patients treated with the conventional fixed orthodontic appliance. Another group consisted of patients treated with clear aligners. Radiographic images were collected with the help of CBCT for each patient. One image was collected before treatment while another image was collected after treatment. The length of the root of the anterior tooth was measured with the help of CBCT images. The ARR was calculated for each tooth by obtaining the difference between the length of the root measured before orthodontic treatment and after orthodontic treatment. The data were recorded, and statistical analysis was carried out with the help of the paired t test and Chi-square test to compare ARR between the two groups. RESULTS: The ARR was more in patients who were treated with fixed orthodontic treatment than in those patients who were treated with clear aligners. The mean value of ARR in fixed orthodontic appliances was 1.51 ± 1.34 mm, whereas the mean value of ARR in clear aligners was 1.12 ± 1.34 mm. The severity of ARR in the clear aligners group (on average) was significantly less than that in the fixed appliances group (on average). It was found that ARR in each individual's tooth included in the study was more in case of the fixed orthodontic appliance as compared with clear aligners (p <0.001). CONCLUSION: From the present study, it can be concluded that the amount of resorption at the root apex is less among patients who undergo treatment using clear aligners as compared with those treated with conventional fixed orthodontics appliances. CLINICAL SIGNIFICANCE: ARR found in the orthodontic treatment is a process that causes loss of hard dental tissues such as dentine and cementum at the root apex. Fixed orthodontic appliances are most common method of orthodontic treatment. However, clear aligners are also used commonly for orthodontic treatment.


Assuntos
Aparelhos Ortodônticos Removíveis , Reabsorção da Raiz , Tomografia Computadorizada de Feixe Cônico , Humanos , Aparelhos Ortodônticos Fixos , Projetos de Pesquisa , Reabsorção da Raiz/diagnóstico por imagem , Reabsorção da Raiz/etiologia
4.
Bioessays ; 40(2)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29250807

RESUMO

Many targets of the Wnt/ß-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a "transcriptional switch," repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway.


Assuntos
Regulação da Expressão Gênica , Fatores de Transcrição TCF/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Animais , Humanos , Proteínas Repressoras/genética , Ativação Transcricional , Ubiquitinação
5.
J Contemp Dent Pract ; 21(5): 494-499, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32690830

RESUMO

AIM: This study aimed to compare the effects of subgingival delivery of 2% curcumin gel and 0.2% chlorhexidine gel as an adjunct to scaling and root planing (SRP) on clinical and microbiological parameters in the management of patients with chronic periodontitis. MATERIALS AND METHODS: In total, 25 systemically healthy individuals with age group ≥30 years diagnosed with chronic periodontitis were included in the study. The study was a double-blind split-mouth randomized control clinical trial. Two sites were selected in each patient and were randomly allocated to experimental and control sites. At baseline, measurements of site-specific periodontal parameters and collection of subgingival plaque sample were done. After full-mouth SRP, subgingival delivery of 2% curcumin gel in experimental sites and 0.2% chlorhexidine gel in control sites was done. At 1 and 3 months, subgingival plaque samples were collected again and site-specific periodontal parameters were measured. RESULTS: The experimental group (2% curcumin gel) showed statistically significant improvements in periodontal [i.e., sulcus bleeding index (SBI), probing pocket depth (PPD), and relative attachment level (RAL)] and microbiologic parameters in the form of colony-forming units (CFUs) in comparison with control group (0.2% chlorhexidine gel). CONCLUSION: Subgingival delivery of curcumin has shown effective anti-inflammatory and antibacterial properties. Since it is biologically accepted by the patients and its delivery in periodontal pockets can be recommended as an adjunct to SRP therapy for the treatment of patients with localized, moderate chronic periodontitis and in patients under the periodontal maintenance phase. CLINICAL SIGNIFICANCE: Curcumin being a herbal agent may be excellent alternative to chlorhexidine. It is biologically accepted by the patients and can be recommended as an adjunct to SRP in the treatment of localized moderate chronic periodontitis and periodontal maintenance patients.


Assuntos
Anti-Infecciosos Locais , Periodontite Crônica , Curcumina , Clorexidina , Raspagem Dentária , Humanos , Aplainamento Radicular
6.
Circ Res ; 114(11): 1733-42, 2014 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-24647144

RESUMO

RATIONALE: The efflux capacity of high-density lipoprotein (HDL) with cultured macrophages associates strongly and negatively with coronary artery disease status, indicating that impaired sterol efflux capacity might be a marker-and perhaps mediator-of atherosclerotic burden. However, the mechanisms that contribute to impaired sterol efflux capacity remain poorly understood. OBJECTIVE: Our aim was to determine the relationship between myeloperoxidase-mediated oxidative damage to apolipoprotein A-I, the major HDL protein, and the ability of HDL to remove cellular cholesterol by the ATP-binding cassette transporter A1 (ABCA1) pathway. METHODS AND RESULTS: We quantified both site-specific oxidation of apolipoprotein A-I and HDL's ABCA1 cholesterol efflux capacity in control subjects and subjects with stable coronary artery disease or acute coronary syndrome. Subjects with coronary artery disease and acute coronary syndrome had higher levels of chlorinated tyrosine 192 and oxidized methionine 148 compared with control subjects. In contrast, plasma levels of myeloperoxidase did not differ between the groups. HDL from the subjects with coronary artery disease and acute coronary syndrome was less able to accept cholesterol from cells expressing ABCA1 compared with HDL from control subjects. Levels of chlorinated tyrosine and oxidized methionine associated inversely with ABCA1 efflux capacity and positively with atherosclerotic disease status. These differences remained significant after adjusting for HDL-cholesterol levels. CONCLUSIONS: Our observations indicate that myeloperoxidase may contribute to the generation of dysfunctional HDL with impaired ABCA1 efflux capacity in humans with atherosclerosis. Quantification of chlorotyrosine and oxidized methionine in circulating HDL might be useful indicators of the risk of cardiovascular disease that are independent of HDL-cholesterol.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Aterosclerose/metabolismo , Colesterol/metabolismo , Lipoproteínas HDL/metabolismo , Peroxidase/metabolismo , Transdução de Sinais/fisiologia , Síndrome Coronariana Aguda/metabolismo , Síndrome Coronariana Aguda/fisiopatologia , Idoso , Apolipoproteína A-I/metabolismo , Aterosclerose/fisiopatologia , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Masculino , Metionina/metabolismo , Pessoa de Meia-Idade , Oxirredução
7.
J Pharm Bioallied Sci ; 16(Suppl 2): S1808-S1810, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882812

RESUMO

Background: Class II malocclusions are a common orthodontic problem, often requiring comprehensive treatment to achieve proper occlusion and facial harmony. Early orthodontic intervention in the mixed dentition phase has been advocated to address these issues. Materials and Methods: A retrospective analysis was conducted on a cohort of 150 patients with class II malocclusions who underwent early orthodontic treatment between the ages of 7 and 10 years. The treatment included fixed or removable appliances, headgear, and functional appliances, depending on individual needs. Records of their initial malocclusion severity, treatment modalities, and long-term follow-up data (mean follow-up duration of 10 years) were collected and analyzed. Stability was assessed by evaluating overjet and overbite changes from post-treatment to the long-term follow-up. Results: The initial mean overjet and overbite values were 8.5 mm and 4.0 mm, respectively. Following early orthodontic intervention, these values were significantly reduced to 3.0 mm and 1.5 mm, respectively (P < 0.001). At the long-term follow-up, the mean overjet and overbite remained stable at 3.2 mm and 1.6 mm, respectively. Analysis revealed that 85% of patients maintained their corrected class II occlusion within clinically acceptable limits, while 15% experienced minor relapse requiring minimal additional treatment. Conclusion: Early orthodontic treatment in class II malocclusions can lead to significant improvements in overjet and overbite, and these corrections tend to remain stable over the long term.

8.
J Pharm Bioallied Sci ; 16(Suppl 2): S1805-S1807, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882826

RESUMO

Background: Accelerated orthodontic treatment has gained popularity in recent years as patients seek shorter treatment durations. Microosteoperforations (MOPs) have emerged as a minimally invasive technique to expedite tooth movement. This study aims to compare the effectiveness of MOPs in accelerating orthodontic treatment with conventional methods. Materials and Methods: A randomized controlled trial was conducted on 60 orthodontic patients requiring dental alignment. The participants were divided into two groups: Group A (MOPs) and Group B (conventional orthodontic treatment). In Group A, MOPs were performed at the beginning of the treatment. Both groups received monthly orthodontic adjustments. Treatment duration, rate of tooth movement, and patient discomfort were measured and compared between the two groups. Results: The study found that in Group A, the treatment duration was reduced by 30% compared to Group B (P < 0.05). The rate of tooth movement in the MOPs group was 1.5 times higher than the conventional group (P < 0.01). Additionally, patient-reported discomfort levels were similar between the two groups. No adverse events related to MOPs were observed during the study. Conclusion: MOPs significantly accelerate orthodontic treatment, reducing treatment duration by 30% and increasing the rate of tooth movement by 1.5 times compared to conventional methods. Importantly, MOPs are well-tolerated by patients, making them a valuable option for expediting orthodontic treatment with minimal discomfort. This study highlights the potential benefits of integrating MOPs into orthodontic practice to improve treatment efficiency and patient satisfaction.

9.
J Basic Clin Physiol Pharmacol ; 35(1-2): 79-84, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38468505

RESUMO

OBJECTIVE: The objective of our study was to assess the impact of heat stress on hydration and cognition among outdoor workers in hot environment. METHODS: Area heat stress assessments were measured using Quest Temp WBGT monitor. Sweat rate for dehydration and reaction time for acute cognitive processing were recorded using standard procedures. RESULTS: Heat stress measurements ranged from 23.8 °C - 42 °C. More than 50 % of the workers had high sweat rate (>1.2 L/h) when exposed to high environmental temperatures. Positive correlation was obtained between WBGT, sweat rate and reaction time which indicates that hyperthermia has an impact on neural network processing. Heart rate and reaction time also increased with rise in WBGT and heavy physical activity. CONCLUSIONS: There was impairment of cognitive functions (reaction time) under heat stress conditions. Hence, reaction time can be used to assess the short-term impact of heat stress on neural modulation and will help to plan effective intervention strategies to reduce morbidity and mortality among workers.


Assuntos
Transtornos de Estresse por Calor , Exposição Ocupacional , Humanos , Temperatura Alta , Exposição Ocupacional/efeitos adversos , Temperatura , Resposta ao Choque Térmico , Índia
10.
Bioinformation ; 19(8): 881-885, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908614

RESUMO

Excessive heat generation during bone drilling for dental implant placement is a known risk factor for bone necrosis and delayed healing. Therefore, it is of interest to evaluate the maximum change in temperature during and after preparation of the implant site for an implant diameter of 4.2 using gradual drilling and single drilling protocols. Hence, 26 artificial bone blocks with d1 density were divided into two groups where the group I had 13 sites prepared using a single drill and for group II bone blocks, 13 implant sites were prepared with the gradual drill protocol using 5 drills. The drill was done at room temperature with 1500 rpm using constant saline irrigation of 50ml/min. The maximum change in temperature was assessed using an intraoral camera. The data collected were statistically evaluated and results were formulated. Data shows that temperature change was significantly higher in group II where a gradual drill protocol was done compared to group I with a single drill protocol for placing the dental implant of diameter 4.2.Considering its limitations, the present in-vitro assessment concludes that a single drill protocol for preparing an osteotomy site for placing a dental implant of diameter 4.2 generates lesser heat than conventional gradual drilling protocols.

11.
Cureus ; 15(7): e42584, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37637545

RESUMO

Background A range of diseases affecting the jaw muscles and/or temporomandibular joint are referred to as temporomandibular disorders (TMDs). Nearly 80% of the general population is affected by TMDs, and 48% of those people have trouble opening their mouths and have painful muscles. Aim To compare the effectiveness of transcutaneous electrical nerve stimulation (TENS) and microcurrent nerve stimulation (MENS) for the relief of masticatory muscle discomfort. Methods Groups I and II were further separated into two groups of 30 persons each (A and B), as well as subgroups C and D. Subjects in Group I received TENS treatment for 20 minutes at frequencies of 0-5 and 5-5 for subgroups A and B, and with visual analog scale (VAS) scores of 1-5 and 6-10 for subgroups C and D, respectively. Subjects in Group II received MENS for 20 minutes, with subgroups C and D receiving the same frequency and VAS score as subgroups A and B, respectively. All individuals underwent treatment with a comparable frequency and length of time every day for five days. Results For subgroup D treated with MENS, there was a considerable reduction in pain; however, for subgroups A and C, there was a comparable reduction in the VAS score for both groups treated with MENS and TENS therapy. Conclusion Compared to TENS, MENS provides quicker and more effective pain relief. Paresthesia and tingling are two adverse effects of TENS that are not present with MENS. However, MENS and TENS are equally helpful at treating masticatory muscle discomfort that is both acute and chronic, as well as improving mouth opening.

12.
Cureus ; 15(7): e42101, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37602008

RESUMO

OBJECTIVES: Rheumatoid arthritis (RA) has been defined by the American College of Rheumatology in 1987 as a chronic inflammatory disease characterised by joint swelling, joint tenderness, and destruction of synovial joints leading to severe disability and premature mortality. There is a paucity of literature assessing corticomotor excitability in RA patients. This study aimed to assess the effect of motor imagery on corticomotor excitability and pain status in RA patients. The specific objectives were to study the effect of motor imagery on corticomotor excitability and pain status in RA patients. We also wanted to compare the corticomotor excitability between RA patients with healthy controls. The correlation between the measures of corticomotor excitability and pain status in RA patients has also been done. METHODS: The study was designed as a pilot clinical trial with a case-control design. Forty participants were recruited for the study. Twenty RA patients were recruited from the Department of Rheumatology and Department of Physical Medicine and Rehabilitation (PMR), AIIMS, New Delhi, and 20 healthy controls. Testing was performed at the Pain Research & rTMS Lab, Department of Physiology, AIIMS, New Delhi. The study was approved by the Institute Ethics Committee, AIIMS New Delhi, and registered in the Clinical Trials Registry-India (CTRI). For the subjective assessment of pain, the visual analogue scale (VAS), Short-Form McGill Pain Questionnaire, WHO-Quality of Life Brief questionnaire (WHO-QOL-BREF), and Rheumatoid Arthritis Pain Scale were used. For the objective assessment of pain, hot and cold pain thresholds were assessed using thermo-tactile quantitative sensory testing (QST) using the method of limits and corticomotor excitability using a transcranial magnetic stimulation device. All participants were also asked to perform motor imagery tasks which consisted of a metronome-paced thumb opposition paradigm.  Results: The resting motor threshold (RMT) decreased significantly after motor imagery when compared to the mental calculation group. The amplitude of motor evoked potential (MEP) and QST parameter value was comparable in both the groups before and after motor imagery and mental calculation. RMT was found to be significantly higher whereas MEP values were found to be significantly lower in RA compared to controls. CONCLUSION: We conclude that patients suffering from RA have decreased corticomotor excitability compared to controls. Motor imagery was effective in improving corticomotor excitability in these patients and can be used as rehabilitation in RA to relieve their pain.

13.
Cureus ; 15(7): e42309, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37614253

RESUMO

BACKGROUND: Previous literature data has extensively assessed the biocompatibility of various orthodontic adhesives and their components, where the results of most of the studies showed cytotoxic effects of different degrees owing to the unbound molecules released structurally from the cured components. AIM: The present in-vitro study was aimed to assess the release of titanium dioxide nanoparticles in the artificial saliva from the orthodontic composites impregnated with titanium dioxide nanoparticles of 5% w/w (weight/weight) and 1% w/w used for metal brackets bonding. METHODS: The study assessed 160 teeth extracted freshly during orthodontic treatment and divided into two groups of 80 samples, each that bonded to orthodontic brackets having 5% w/w and 1% w/w composites with titanium dioxide nanoparticles kept in the artificial saliva. Quantification was done for 5% w/w and 1% w/w composites having titanium nanoparticles with inductively coupled plasma mass spectroscopy at 24 hours, two, four, and six months. RESULTS: It was seen that in teeth with 1% titanium dioxide, the greatest titanium release was seen at two months, with non-significant release after two months. In teeth with 5% w/w titanium dioxide nanoparticles showed significant titanium release all the time. A significantly greater titanium dioxide release on increasing concentration from 1% to 5% was seen for the 5% w/w group at all the assessment times. CONCLUSION: The present study concludes that a higher release of titanium is seen in 5% w/w composite containing titanium dioxide nanoparticles, and the concentrations of 1% and 5% can be safely used and are considered to be within permissible limits.

14.
Cureus ; 15(7): e42035, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37593263

RESUMO

BACKGROUND:  Oral cancer is a rapidly growing disease among Indian subjects mainly in the low socioeconomic group. Socially and economically marginalized subjects are at high risk for oral cancer because of smoke and smokeless tobacco consumption. AIM:  To evaluate the prevalence of precancerous lesions and oral cancer and evaluate tobacco as a causative factor in Indian subjects visiting the outpatient department of the institute. METHODS:  Around 658 subjects were analyzed for frequency of premalignant lesions and oral malignancy in Indian subjects from the low socioeconomic group. Patients visited for pain, burning, or ulceration in the oral cavity were clinically assessed for any tissue growths, leathery alterations, ulcerative changes, and white or red lesions in the oral cavity.  Results: The overall prevalence of smokeless and smoking tobacco was 78.8% (n=518) and 65.2% (n=429) respectively in the present study. Around 39.8% (n=262) of samples were stained positive for precancerous and cancerous lesions of the oral cavity. The highest number of positive samples were from buccal mucosa with 36.2% (n=238) subjects and 6.1% (n=40) for labial mucosa. CONCLUSIONS:  Oral cancer is highly prevalent in Indian subjects owing to high tobacco consumption rates and habits warranting the cessation center a priority. Also, early detection and screening are vital to attaining better outcomes. More tobacco cessation centers are needed to stop the habit and early diagnosis will prevent dysplastic changes.

15.
Nat Biotechnol ; 41(1): 82-95, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36109686

RESUMO

Accurate identification and effective removal of unwanted variation is essential to derive meaningful biological results from RNA sequencing (RNA-seq) data, especially when the data come from large and complex studies. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we examined several sources of unwanted variation and demonstrate here how these can significantly compromise various downstream analyses, including cancer subtype identification, association between gene expression and survival outcomes and gene co-expression analysis. We propose a strategy, called pseudo-replicates of pseudo-samples (PRPS), for deploying our recently developed normalization method, called removing unwanted variation III (RUV-III), to remove the variation caused by library size, tumor purity and batch effects in TCGA RNA-seq data. We illustrate the value of our approach by comparing it to the standard TCGA normalizations on several TCGA RNA-seq datasets. RUV-III with PRPS can be used to integrate and normalize other large transcriptomic datasets coming from multiple laboratories or platforms.


Assuntos
Neoplasias , RNA , Humanos , Perfilação da Expressão Gênica/métodos , Análise de Sequência de RNA , Neoplasias/genética
16.
J Oral Maxillofac Pathol ; 26(4): 568-571, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37082064

RESUMO

Mucosal malignant melanoma arising from the head and neck region is a rare entity, and it is more aggressive than cutaneous melanoma. Furthermore, the complexity of the oral cavity makes surgical excision more difficult. Oral malignant melanoma is a rare tumour of melanocytic origin, accounting for 20-30% of malignant melanomas at the mucosal surface and 16% intra-orally. Hard palate and maxillary gingiva are the most common involved sites. The age of reported patients ranges from 20 years to 80 years. Hence, we do hereby present a case of malignant melanoma of mandibular gingiva with review of the literature in a 42-year-old female patient.

17.
Cureus ; 14(10): e30156, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36397922

RESUMO

BACKGROUND:  Disturbances seen during tooth formation result in developmental dental anomalies presenting in the oral cavity. These anomalies manifest as discrepancies in the number, color, size, and shape of the teeth. These dental anomalies can either be acquired, congenital, or developmental. Their early detection and management are necessary as they affect aesthetics and occlusion. The study had the aim of gauging the prevalence of developmental anomalies in the permanent dentition of Indian subjects. METHODS: A total of 1192 participants recruited from the institute for study purposes, comprising males and females, were examined clinically and radiographically, and their dental casts were also evaluated. These subjects were assessed for anomalies in position, structure, number, and/or shape. Anomalies in the position include transmigration, transportation, and/or ectopic position; anomalies in the structure, including dentinogenesis imperfecta or amelogenesis imperfecta; anomalies in number, including hyperdontia or hypodontia; and anomalies in shape, including peg laterals, taurodontism, fusion, dens evaginatus, talon cusp, and/or microdontia. RESULTS: A statistically significant difference was seen in unilateral microdontia and dentinogenesis imperfecta between males and females, with attained p-values of 0.003 and 0.06, respectively. The results of the present study showed that 9.89% (n = 118) study subjects, whereas 1% (n = 12) study subjects had two dental anomalies in their permanent dentitions, with no subject presenting more than two dental anomalies, showing that various dental anomalies have a low prevalence in the Indian population. CONCLUSION: The present study has led to the conclusion that the prevalence of dental anomalies is low in Indian subjects. However, these anomalies should be detected and treated early to prevent them from causing further complications.

18.
Cureus ; 14(11): e31735, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37377463

RESUMO

BACKGROUND: Literature worldwide has linked periodontitis to preterm births and/or low-birth-weight infants. However, to our knowledge, research on this topic is scarce in India. The United Nations Children's Fund (UNICEF) reports that South Asian nations, particularly India, have the highest rates of preterm births and low-birth-weight infants as well as periodontitis due to poor socioeconomic conditions. Overall, 70% of perinatal fatalities result from prematurity and/or low birth weight, which also increases the incidence of morbidity and drives up the cost of postpartum care by a factor of ten. The frequency and severity of the illness may be greater among the Indian population due to their poor socioeconomic status. To lower the mortality rate and the cost of postnatal care, it is necessary to investigate the impact and severity of the effect of periodontal conditions on pregnancy outcomes in India. MATERIALS AND METHODS: Following the collection of obstetric and prenatal records from the hospital in compliance with inclusion and exclusion criteria, a sample of 150 pregnant women were chosen from public healthcare clinics for the research. Within three days of delivery following enrolment in the trial, a single physician recorded each subject's periodontal condition using the University of North Carolina-15 (UNC-15) probe under artificial lighting and the Russell periodontal index. The gestational age was calculated based on the latest menstrual cycle, and a medical professional would order an ultrasound if they felt it was essential. The doctor weighed the newborns soon after delivery and in accordance with this prenatal record. The acquired data was analyzed using a suitable statistical analysis technique. RESULTS: The severity of a pregnant woman's periodontal disease was significantly correlated with the infant's birth weight and gestational age. Preterm births and low-birth-weight infants became more prevalent as the severity of the periodontal disease rose. CONCLUSION: The results demonstrated that periodontal disease in pregnant women may increase the risk of preterm delivery and low birth weight in infants.

19.
J Family Med Prim Care ; 11(11): 7036-7041, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36993129

RESUMO

Background: The purpose of this study was to measure primary health care providers' understanding of the significance of health literacy and self-efficacy in cigarette quitting. Material and Methods: The current study used a quantitative descriptive questionnaire to collect data. The research was carried out among primary health care providers in a rural location near the Azamgarh Dental College in Uttar Pradesh. Medical officials, nursing personnel, and dental practitioners, if existent, are examples of primary health professionals. Azamgarh district is divided into 22 blocks. 22 primary health facilities were selected from these 22 blocks. 54 medical officers and 98 other primary health workers (ANMs, GNMs, and Asha workers) were questioned at these primary health facilities. Results: The majority of study participants {132 (86.84%)} were aware of the bad effects of tobacco consumption. Most of the study participants don't know about health literacy {115 (75.65%)} and self-efficacy {78 (51.32%)}. The majority of them did not know the questionnaire to test health literacy {114 (75.02%)} and self-efficacy {150 (98.68%)}. poor mean awareness score (20.77 ± 3.33) was significant (p = 0.001) in the age group 25-35 years. Anganwadi workers were having significantly (p = 0.002) highest poor awareness score (22.67 ± 2.34). Conclusion: From the above results, it was concluded that awareness of the role of health literacy and self-efficacy in tobacco cessation among primary health workers was poor. Almost all study participants had not attended any training programs on tobacco cessation.

20.
Transl Oncol ; 21: 101426, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35460943

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common non-skin cancer with a tobacco consumption and infection with high-risk human papillomavirus (HPV) being major risk factors. Despite advances in numerous therapy modalities, survival rates for HNSCC have not improved considerably; a vast number of clinical outcomes have demonstrated that a combination strategy (the most well-known docetaxel, cisplatin, and 5-fluorouracil) is the most effective treatment choice. Immunotherapy that targets immunological checkpoints is being tested in a number of clinical trials, either alone or in conjunction with chemotherapeutic or targeted therapeutic drugs. Various monoclonal antibodies, such as cetuximab and bevacizumab, which target the EGFR and VEGFR, respectively, as well as other signaling pathway inhibitors, such as temsirolimus and rapamycin, are also being studied for the treatment of HNSCC. We have reviewed the primary targets in active clinical studies in this study, with a particular focus on the medications and drug targets used.

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