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1.
Cureus ; 16(6): e63025, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39050292

ABSTRACT

Introduction The unique nature of a lack of good oral health, coupled with the lack of discussion and recognition surrounding the associated stigma, highlights it as a distinct issue. This stigma causes discomfort, devalues individuals, and necessitates urgent care and intervention. In Pakistan, a variety of reasons, including cultural beliefs, socioeconomic gaps, and poor access to dental care services, tend to exacerbate the stigma that is associated with dental care. This study aimed to determine the impact of stigma on oral health-seeking behaviours amongst the population of South Punjab in Pakistan. Methodology The study employed a qualitative design with a phenomenological approach, and the data collection was preceded by the administration of semi-structured interview guides and discussion guides to the patients and the consultant group, respectively. The targeted population was composed of patients who had reported stigmatization and a focus group of 10 dental consultants from various specialisations in dentistry. Data was collected until saturation from 16 patients who were recruited through the purposive convenience sampling technique. Results The study identified three themes, including perceived stigma impact on health-seeking behaviours and coping mechanisms; 10 subthemes emerged. Results showed social attitudes and unhealthy perceptions of oral conditions that lead to shame, loss of self-esteem, and lack of confidence among affected individuals. Behavioural reactions like mockery and discrimination further made it difficult for the participants who sought dental care and treatment. The study highlighted that stigma resulted in the avoidance of dental care, deterioration of oral health, and a tendency towards self-medication. People also used coping strategies such as hiding dental issues by avoiding social gatherings and seeking help from close friends to manage oral health stigma. Dental consultants had the strong opinion that care quality could be enhanced by utilising compassionate communication and patient education campaigns. Conclusions The experiences of patients and consultants related to dental stigma highlighted the complex interplay of sociocultural norms and healthcare practices. The study demonstrated that perceived stigma impacted the health-seeking behaviours of patients. Social support and education about oral health helped patients overcome this stigma. The study revealed that patients avoided dental treatments due to stigmatised behaviour from health professionals, a lack of affordability, and a feeling of shame to show and discuss the condition of their teeth, which got even worse due to self-remedy. The experiences of patients and consultants highlighted the need for increased advocacy, educational campaigns, and policies that can reduce inequalities in oral health and improve health equity. The study recommends specific intervention strategies and policy formulation to address oral health inequalities and contribute to advancing oral health equity in Pakistan.

2.
ACS Omega ; 9(12): 14043-14053, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38559943

ABSTRACT

Substantial efforts have been made to design and investigate new approaches for high-performance nonlinear optical (NLO) materials. Herein, we report polaron formation in conducting polymers as a new approach to designing materials with a large NLO response. A comparative study of polypyrrole and polypyrrole-based polaron (nPy+ where n = 1, 3, 5, 7, and 9) is carried out for optoelectronic and NLO properties. The studied polarons (PPy+) show excellent electronic properties and have reduced ionization potential (IP) as compared to neutral PPy, and a monotonic decrease is observed with increased chain lengths (1Py to 9Py). Interesting trends of global reactivity descriptors can be seen; the softness (S) increases with an increase in the chain length of PPy, while the hardness (η) decreases in the same fashion. The EH-L gaps for the PPy+ polaronic state are significantly lower than their corresponding neutral PPy. In the polaronic model (PPy+), radicals decisively reduce the crucial excitation energy, reminiscent of excess electrons (alkali metals). The performed TDOS spectral analysis further justifies the better conductive and electronic properties of polarons (PPy+) with increased chain lengths (conjugation). The static hyperpolarizability response (ßo) is recorded up to 1.3 × 102 au for 9Py, while for polaron 9Py+, it has increased up to 3.2 × 104 au. The static hyperpolarizability of the 9Py+ polaronic state is 246 times higher than that of the corresponding neutral analogue, 9Py. It is observed that the values of ßo obtained at the CAM-B3LYP/6-311+G(d,p) level of theory are comparable to those obtained at the LC-BLYP and ωB97XD functionals. The ßvec values show a strong correlation with the total hyperpolarizability (ßo). Furthermore, the calculated second harmonic generation (SHG) values are up to 4.0 × 106 au at 532 nm, whereas electro-optic Pockel's effect (EOPE) is much more pronounced at the smaller dispersion frequency (1064 nm). The TD-DFT study reveal the red-shifted absorption maxima (λmax) with an increased length of PPy+. A significant reduction in excitation energy (ΔE) is observed with increased length of PPy and PPy+, which also favors the improved NLO response. Hence, the studied thermally conducting polypyrrole-based polarons (PPy+) are new entries into NLO materials with better electrical and optical features.

3.
Steroids ; 185: 109059, 2022 09.
Article in English | MEDLINE | ID: mdl-35679910

ABSTRACT

Breast cancer (BCa) is very common malignancy and globally, has become the second leading cause of cancer death among women. For the treatment of BCa, estrogen receptors-alpha (ERα) has proven to be a therapeutic target. In continuation of our previous reported dihydropyrimidine-based pregnenolone derivatives, we modified at C-3 hydroxyl group. Structural architecture of estrogen receptors (ER) with excellent ER binding affinity was used for modification. MTT assay was used to evaluate the synthesized steroidal analogs for their antiproliferative activities against ER-positive MCF-7, ER-negative MDA-MB-231 (ER-) breast cancer cells and non-cancerous HEK-293 cells. Structure activity relationship (SAR) studies revealed that diethanolamine containing pregnenolone derivatives showed significant cytotoxicity against ER + MCF-7 and also showed good binding affinity with ERα and are relatively safe against HEK-293 cell model. Docking studies demonstrated that high binding affinity of diethanolamine analogs is due to their binding interaction with key amino acid residues present in the binding site of Erα.


Subject(s)
Breast Neoplasms , Estrogen Receptor alpha , Breast Neoplasms/metabolism , Cell Proliferation , Estrogen Receptor alpha/metabolism , Female , HEK293 Cells , Humans , MCF-7 Cells , Pregnenolone/pharmacology , Pregnenolone/therapeutic use , Receptors, Estrogen/metabolism
4.
Bioorg Med Chem Lett ; 64: 128668, 2022 05 15.
Article in English | MEDLINE | ID: mdl-35276362

ABSTRACT

Based on the structural architecture of estrogen receptors (ER) agonists/antagonists, we rationally designed and synthesized indenopyrimidine-2,5-dione analogs as a starting point of current research targeting estrogen receptors. These analogs were evaluated for their antiproliferative activities against breast cancer MCF-7 (ER+), MDA-MB-231 (ER-) and non-cancerous HEK-293 cells using MTT assay. Compounds with high antiproliferative activity against MCF-7 breast cancer cells were found devoid of cytotoxicity against HEK-293 cells. Competitive binding assay of estrogen receptors ERα and ERß showed that diethanolamine derivative of 4-trifluoromethyl phenyl derivative 30 displayed 77.5-fold strong binding affinity towards ERα (IC50 = 0.004 µM) as compared to ERß (IC50 = 0.31 µM). The calculated RBA value of compound 30 indicated that it has greater affinity with ER than estradiol. By docking studies, we demonstrated that high binding affinity with ERα is due to binding orientation and interaction of CF3 with a number of key amino acid residues present in the active site of ERα.


Subject(s)
Breast Neoplasms , Receptors, Estrogen , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cell Proliferation , Estradiol , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Female , HEK293 Cells , Humans , MCF-7 Cells , Receptors, Estrogen/metabolism
5.
J Pak Med Assoc ; 69(11): 1687-1692, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31740880

ABSTRACT

Wingless-Integrated/Beta-catenin (WNT/-catenin) signalling pathway is one of the principal intercellular signalling pathways in humans. It plays an intrinsic role in the cellular proliferation, differentiation and regeneration along with many other cellular functions. Epigenetic deoxyribonucleic acid methylations and silencing of WNT signalling pathway genes have a significant role in malignant transformation of oral lesions such as oral submucous fibrosis, oral leukoplakia, oral lichen planus and erythroplakia. The increase in WNT inhibitory proteins along with inflammatory factors cause bone loss in periapical lesions, such as chronic apical periodontitis. This review discusses the molecular genetics of potentially malignant oral lesions, sheds light on our understanding of WNT/-catenin signalling in bone loss pertaining to periapical lesions, and alteration of this pathway for therapeutic benefits.


Subject(s)
Mouth Neoplasms , Wnt Signaling Pathway , Bone Diseases , Carcinogenesis , Humans , Mouth Diseases , Periapical Diseases
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