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Targeting phosphoglycerate dehydrogenase enzyme using ginger compounds to suppress thyroid cancer progression Rahman, Faris I.; Zulfa, Putri O.; Beočanin, Anđelija; Faisal, Ibraheem M.; Louca, Nicolas; Carstoiu, Maria I.; Zufry, Hendra
Narra X Vol. 2 No. 1 (2024): April 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narrax.v2i1.112

Recent studies have recognized the potential of inhibiting phosphoglycerate dehydrogenase (PHGDH) enzyme as a therapeutic strategy for treating papillary thyroid cancer. However, research on the efficacy of herbal compounds in inhibiting the PHGDH enzyme that have been reported to possess anticancer activities, including those found in ginger (Zingiber officinale), remains limited. The aim of this study was to examine the potential of ginger compounds in inhibiting PHGDH enzyme and to identify its potential use in the treatment of papillary thyroid cancer. The study employed computational methods to identify ginger-derived compounds that inhibit the PHGDH and impede papillary thyroid cancer progression. Crystallized protein structures were obtained from the Protein Data Bank, and Discovery Studio software was utilized to remove water molecules, double chains, and ligands. The receptor was modified by adding polar hydrogen, and AutodockTools4 software was employed to establish an accurate binding site based on the position of the previous ligand. Molecular docking experiments were conducted with 125 ginger-derived phytochemicals retrieved from the PubChem database. The results revealed nine active compounds found in ginger (galanolactone, myricetin, quercetin, cyanin, kaempferol, chlorogenic acid, delphinidin, alpha-cadinol, and curcumin) with strong binding affinities to PHGDH (minimum score threshold <-7 kcal/mol), indicating their potential for drug development. Galanolactone, myricetin, and quercetin were the top three compounds with the strongest binding affinity (-8.2, -7.9, and -7.9 kcal/mol, respectively), involving multiple bonds in the ligand-protein complex interaction. Notably, myricetin and quercetin formed three hydrogen bonds each, contributing to strong and stable bonds with the pocket region of PHGDH. In conclusion, ginger-derived compounds show promise in inhibiting PHGDH for the treatment of papillary thyroid cancer. However, further research is needed to validate the efficacy of these compounds and their interactions with the PHGDH in the context of thyroid cancer therapy.

Normal intellectual ability and hyperprolactinemia as unique clinical manifestations of congenital hypothyroidism: A case report and review of hypotheses Zulfa, Putri O.; Debbyousha, Maulina; Sucipto, Krishna W.; Ekadamayanti, Agustia S.; Firdausa, Sarah; Zufry, Hendra
Narra J Vol. 3 No. 3 (2023): December 2023
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v3i3.205

Congenital hypothyroidism is the deficiency of thyroid hormone in infants and hyperprolactinemia is frequently observed. Previously reported cases typically involve intellectual disability, highlighting this particular unique case report to the first reported patient demonstrating normal intellectual ability despite experiencing growth and gonad dysfunction. This study aims to present a case and review medical hypotheses related to the patient's condition. A 19-year-old female presented with a chief complaint of irregular menstruation for up to 40 days or not occurring at all. The patient experienced the first menstruation at the age of 16 years old. The patient's height was 133 cm, body weight 40 kg, and body mass index 22.61 kg/m2; other family members were normal. Physical examination showed no abnormalities, and laboratory examination showed suppressed serum free T4 (FT4) level (6.41 pmol/L), elevated thyroid stimulating hormone (TSH) level (333.700 µIU/mL), and elevated prolactin hormone level (32.03 ng/mL). Ultrasound of the thyroid gland found hypoplasia of the left and right thyroid glands. The patient was a college student enrolled in a public national university and had never complained about academic performance throughout the patient's education. The patient was diagnosed with congenital hypothyroidism and hyperprolactinemia. The patient was administered up to 100 μg daily of oral levothyroxine, which improved the patient’s menstrual cycles. The patient's delayed diagnosis may be attributed to central congenital hypothyroidism being underdiagnosed. We hypothesized that thyroid-releasing hormone receptor (TRHR) gene mutation might contribute to the underlying cause of hyperprolactinemia and normal intellectual ability of the patient. Further study on the significance of TRHR gene mutations in congenital hypothyroidism is required to improve diagnosis and treatment.

Comparative analysis of accuracy between fine-needle aspiration biopsy and postoperative histopathology for detecting large thyroid nodules: A retrospective observational study Zufry, Hendra; Nazaruddin, Nazaruddin; Zulfa, Putri O.; Sucipto, Krishna W.; Kamarlis, Reno K.; Ekadamayanti, Agustia S.; Beočanin, Anđelija; Firdausa, Sarah
Narra J Vol. 3 No. 2 (2023): August 2023
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v3i2.206

To avoid unnecessary surgeries, ultrasound-guided fine-needle aspiration biopsy (FNAB) is an effective and reliable procedure for the preoperative evaluation of thyroid nodules. However, there have been only a limited number of studies exploring the ability of preoperative FNAB to distinguish malignancy compared to postoperative histopathology in thyroid nodules larger than 4 cm. The aim of this study was to investigate the diagnostic accuracy of FNAB compared to postoperative histopathology in distinguishing malignancy in thyroid nodules larger than 4 cm. A single-center retrospective observational study was conducted at Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia, between January 2014 and December 2018. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. A total of 83 patients were included in the study. The results showed that preoperative FNAB may have the ability to distinguish malignancy compared to postoperative histopathology. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 42.85%, 98.38%, 90.00%, 83.56%, and 84.33%, respectively. These data suggested that ultrasound-guided preoperative FNAB is a reliable diagnostic tool in the preoperative evaluation of thyroid nodules larger than 4 cm, but it has limited capability in distinguishing malignancies. In conclusion, although FNAB may be useful in reducing unnecessary surgeries, histopathology remains the preferred method for confirming malignancy in thyroid nodules.

Pneumonectomy for severe post-tuberculosis bronchiectasis: A successful of case report and review of the long-term outcome Zulfa, Putri O.; Habibie, Yopie A.
Narra J Vol. 3 No. 3 (2023): December 2023
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v3i3.222

Limited clinical intervention studies highlight the absence of evidence-based international guidelines for effectively managing post-tuberculosis lung disease, emphasizing bronchiectasis. The aim of this study was to describe a case of left pneumonectomy for severe post-tuberculosis cystic bronchiectasis and to provide a review of the post-surgical mortality rate, complications, survival rate, and the patient's quality of life following the pneumonectomy procedure. A 36-year-old Indonesian male smoker presented with worsening breathing difficulties and fever. The patient had a history of pulmonary tuberculosis six years ago and reported negative tuberculosis tests after completing TB treatment. However, lung function of the patient progressively declined over the years. Bronchoscopy, chest X-ray, and high-resolution computerized tomography (CT) scan revealed infected cystic bronchiectasis and identified a prominent left lung collapse with calcification in the left pleura. The patient underwent left pneumonectomy through left posterolateral thoracotomy under general anesthesia. The patient was discharged after seven post-operative days with no eventful course. No further complications were found after a one-year post-surgery follow-up, and the patient returned to normal activities, improved fitness, and was fitter in daily life. Based on the literature review, post-surgical mortality rates of pneumonectomy are acceptable, with bronchopleural fistula, cardiac arrest, and thoracic hemorrhage being common causes. Yet, the chances of a complete cure are high. Complications can occur in approximately one-third of patients, including arrhythmia, pulmonary infection, fever, and wound infections. The overall 5-year survival rate following pneumonectomy is generally favorable. Regarding the quality of life, pneumonectomy can have mixed effects. While it could improve symptoms and quality of life, it may impair the quality of life for certain patients, particularly elderly patients and those with lower preoperative quality of life. Although the post-surgical mortality rate, complications, and long-term survival rates of pneumonectomy are generally satisfactory, the expectation of improved post-surgical quality of life should be discussed with the patient prior to surgery.

Diagnostic accuracy of preoperative ultrasonography-guided fine-needle aspiration biopsy in distinguishing malignancy in large thyroid nodules: A systematic review, meta-analysis, and meta-regression Zulfa, Putri O.; Iqhrammullah, Muhammad; Zufry, Hendra
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.1120

Controversy persists regarding the effectiveness of ultrasonography-guided fine-needle aspiration biopsy (US-FNAB) in distinguishing malignancies in large thyroid nodules. The prevailing belief that larger thyroid nodules inherently pose a higher risk of malignancy has led to a common practice of suggesting thyroidectomy for large thyroid nodules. Herein, the aim of this study was to assess the diagnostic accuracy of preoperative US-FNAB for distinguishing malignancy in large thyroid nodules. A search for published records was carried out on 20 October 2023, utilizing the search feature available on PubMed, Scopus, Embase, and Google Scholar. Patients with large thyroid nodules (3 cm or larger) who underwent preoperative US-FNAB and postoperative histopathological tests were included. Related outcomes, including false positive (FP), false negative (FN), true negative (TN), true positive (TP), specificity, and sensitivity, were extracted from each study. Pooled specificity and sensitivity were estimated, and the summarized receiver operating characteristic (sROC) curve, along with the summarized area under the curve (sAUC), was calculated. Out of 133 articles identified across four databases, 10 studies with a total sample of 2752 patients were included. The overall diagnostic sensitivity was 72% (95%CI: 50–86%; p=0.00) and specificity was 96% (95%CI: 87–90%; p=0.00). The positive predictive value (PPV) and negative predictive value (NPV) were 93% (95%CI: 89–98%) and 75% (95%CI: 72–79%), respectively. sAUC was 93%, suggesting the diagnostic tool is accurate. Meta-regression analysis revealed that factors such as the number of samples, country (high-income vs upper-middle income), demographic characteristics (age and gender), and different thyroid size cut-off values did not significantly impact the sensitivity or specificity of US-FNAB. In conclusion, the present study confirms the reliability of US-FNAB in distinguishing malignancy in large thyroid nodules, emphasizing its role in reducing unnecessary thyroidectomy by identifying high-risk patients and challenging the conventional practice of routine thyroidectomy for large thyroid nodules.

Targeting phosphoglycerate dehydrogenase enzyme using ginger compounds to suppress thyroid cancer progression Rahman, Faris I.; Zulfa, Putri O.; Beočanin, Anđelija; Faisal, Ibraheem M.; Louca, Nicolas; Carstoiu, Maria I.; Zufry, Hendra
Narra X Vol. 2 No. 1 (2024): April 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narrax.v2i1.112

Recent studies have recognized the potential of inhibiting phosphoglycerate dehydrogenase (PHGDH) enzyme as a therapeutic strategy for treating papillary thyroid cancer. However, research on the efficacy of herbal compounds in inhibiting the PHGDH enzyme that have been reported to possess anticancer activities, including those found in ginger (Zingiber officinale), remains limited. The aim of this study was to examine the potential of ginger compounds in inhibiting PHGDH enzyme and to identify its potential use in the treatment of papillary thyroid cancer. The study employed computational methods to identify ginger-derived compounds that inhibit the PHGDH and impede papillary thyroid cancer progression. Crystallized protein structures were obtained from the Protein Data Bank, and Discovery Studio software was utilized to remove water molecules, double chains, and ligands. The receptor was modified by adding polar hydrogen, and AutodockTools4 software was employed to establish an accurate binding site based on the position of the previous ligand. Molecular docking experiments were conducted with 125 ginger-derived phytochemicals retrieved from the PubChem database. The results revealed nine active compounds found in ginger (galanolactone, myricetin, quercetin, cyanin, kaempferol, chlorogenic acid, delphinidin, alpha-cadinol, and curcumin) with strong binding affinities to PHGDH (minimum score threshold <-7 kcal/mol), indicating their potential for drug development. Galanolactone, myricetin, and quercetin were the top three compounds with the strongest binding affinity (-8.2, -7.9, and -7.9 kcal/mol, respectively), involving multiple bonds in the ligand-protein complex interaction. Notably, myricetin and quercetin formed three hydrogen bonds each, contributing to strong and stable bonds with the pocket region of PHGDH. In conclusion, ginger-derived compounds show promise in inhibiting PHGDH for the treatment of papillary thyroid cancer. However, further research is needed to validate the efficacy of these compounds and their interactions with the PHGDH in the context of thyroid cancer therapy.

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