BACKGROUND

Scabies is a highly contagious neglected tropical disease and a persistent challenge globally, particularly in regions like the Philippines, where it remains endemic. With conventional treatments facing limitations such as resistance and adverse effects, exploring the potential of traditional medicinal plants offers a promising avenue for novel therapeutics. However, evidence of their comparative efficacy and safety is still lacking.

To determine the efficacy and safety of Gliricidia sepium (kakawati), Senna alata (akapulko), and Tinospora rumphii (makabuhay) compared to topical scabicides or placebo in the treatment of Filipino patients with scabies using a systematic review. 

We searched the following databases from inception to March 2024: MEDLINE via PubMed, CENTRAL, EMBASE, EBSCO, HERDIN, ClinicalTrials.gov, WHO-ICRTP, and PHRR. We included all randomized controlled trials involving Filipino patients diagnosed with scabies where preparations containing one of three plants (G. sepium, S. alata, or T. rumphii) were compared with a topical scabicide or placebo for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias (using Risk of Bias 2.0), and extracted data from the included studies. Primary outcomes were complete clearance of skin lesions, reduction of pruritus, and the presence of serious adverse events. Secondary outcomes were recurrence, any adverse events, adverse events requiring withdrawal, and patientreported outcomes. We used RevMan 5.4 to pool dichotomous outcomes using risk ratios and continuous outcomes using mean difference and applied random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi2 test and the I2 statistic. We presented the results using forest plots with 95% confidence intervals. We intended to conduct a funnel plot analysis to check for reporting bias but were unable to because of the limited number of studies. Quality of evidence was assessed using the GRADE approach, and a Summary of Findings table was created using GRADEpro GDT for the primary outcomes.

We included nine RCTs (N=607 participants) that compared various dosage forms (ointments, lotions, poultice, soap, aqueous extract) containing one of the three plants (G. sepium, three studies; S. alata, two studies; T. rumphii, four studies) versus placebo or existing topical scabicides (permethrin, sulfur, crotamiton). Pooled analyses showed that there is probably no difference in complete clearance of lesions between G. sepium and 5% sulfur (RR 0.92 [0.79, 1.07], 2 RCTs, N=85, moderate certainty of evidence). We are uncertain about the difference in complete clearance of lesions between S. alata lotion and placebo (RR 4.94 [1.67, 14.62], 2 RCTs, N=157, very low certainty of evidence), T. rumphii and crotamiton (RR 1.02 [0.76, 1.37], 2 RCTs, N=131, very low certainty of evidence), and T. rumphii lotion and placebo (RR 5.28 [0.76, 36.43], 2 RCTs, N=71, very low certainty of evidence). Data could not be pooled for reduction in pruritus scores due to limited studies for each intervention. No serious adverse events were reported across all studies.

Gliricidia sepium (kakawati) is probably as effective and safe as 5% sulfur in the management of patients with scabies and may be a promising alternative herbal treatment. Future RCTs should compare it with scabicides recommended by the Philippine Department of Health and World Health Organization, such as permethrin, benzyl benzoate or oral ivermectin. T. rumphii and S. alata may also be investigated using RCTs that should be adequately powered and with good methodologic quality.

OBJECTIVE

Manihot esculenta (Crantz) leaves have been used for the management of diabetes based on cited ethnopharmacological studies. However, scientific evidence to support its efficacy is lacking. The aim of the study was to assess the cytotoxicity of the aqueous leaf extract and fractions of Manihot esculenta and its potential hypoglycemic effect on male Swiss albino mice.

The cytotoxicity assay was necessary to screen which extract and fractions will be used for the in vivo hypoglycemic study.

Phytochemical screening identified the composition of the aqueous crude extract and its fractions. The phytochemical results showed the presence of alkaloids, anthraquinone glycosides, carbohydrates, phenolic glycosides, saponins, and flavonoids.

Cytotoxicity was screened using CytoTox 96® (Promega), a NonRadioactive Cytotoxicity Assay on liver cancer (HepG2) and normal kidney (HK-2) cell lines. Five samples were tagged as highly cytotoxic and were flagged for further assays. These samples were DCM fraction (100 ppm), n-Hexane fraction (1 and 10 ppm), Ethyl acetate fraction (1 ppm), and Aqueous fraction (100 ppm).

The hypoglycemic activity was examined in alloxan-induced diabetic mice using in vivo hypoglycemic study. The aqueous crude extract at dose levels of 200 mg/kg and 300 mg/kg body weight showed significant reduction in blood glucose levels compared to the diabetic control but not exceeding the results in the metformin treatment group. A p-value of 0.05 set a priori was used to consider whether the intervention had a statistically significant difference compared to the diabetic control.

The effectiveness of aqueous crude extract in reduction of blood glucose in mice may be attributed to the synergistic effects of phytochemicals present, especially the alkaloids which were retained in the extract but were undetectable in the fractionated samples. The results of this study also support the findings of existing ethnopharmacological studies on M. esculenta leaf extract as a hypoglycemic agent.

BACKGROUND

Scabies is a highly contagious neglected tropical disease and a persistent challenge globally, particularly in regions like the Philippines, where it remains endemic. With conventional treatments facing limitations such as resistance and adverse effects, exploring the potential of traditional medicinal plants offers a promising avenue for novel therapeutics. However, evidence of their comparative efficacy and safety is still lacking.

To determine the efficacy and safety of Gliricidia sepium (kakawati), Senna alata (akapulko), and Tinospora rumphii (makabuhay) compared to topical scabicides or placebo in the treatment of Filipino patients with scabies using a systematic review. 

We searched the following databases from inception to March 2024: MEDLINE via PubMed, CENTRAL, EMBASE, EBSCO, HERDIN, ClinicalTrials.gov, WHO-ICRTP, and PHRR. We included all randomized controlled trials involving Filipino patients diagnosed with scabies where preparations containing one of three plants (G. sepium, S. alata, or T. rumphii) were compared with a topical scabicide or placebo for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias (using Risk of Bias 2.0), and extracted data from the included studies. Primary outcomes were complete clearance of skin lesions, reduction of pruritus, and the presence of serious adverse events. Secondary outcomes were recurrence, any adverse events, adverse events requiring withdrawal, and patientreported outcomes. We used RevMan 5.4 to pool dichotomous outcomes using risk ratios and continuous outcomes using mean difference and applied random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi2 test and the I2 statistic. We presented the results using forest plots with 95% confidence intervals. We intended to conduct a funnel plot analysis to check for reporting bias but were unable to because of the limited number of studies. Quality of evidence was assessed using the GRADE approach, and a Summary of Findings table was created using GRADEpro GDT for the primary outcomes.

We included nine RCTs (N=607 participants) that compared various dosage forms (ointments, lotions, poultice, soap, aqueous extract) containing one of the three plants (G. sepium, three studies; S. alata, two studies; T. rumphii, four studies) versus placebo or existing topical scabicides (permethrin, sulfur, crotamiton). Pooled analyses showed that there is probably no difference in complete clearance of lesions between G. sepium and 5% sulfur (RR 0.92 [0.79, 1.07], 2 RCTs, N=85, moderate certainty of evidence). We are uncertain about the difference in complete clearance of lesions between S. alata lotion and placebo (RR 4.94 [1.67, 14.62], 2 RCTs, N=157, very low certainty of evidence), T. rumphii and crotamiton (RR 1.02 [0.76, 1.37], 2 RCTs, N=131, very low certainty of evidence), and T. rumphii lotion and placebo (RR 5.28 [0.76, 36.43], 2 RCTs, N=71, very low certainty of evidence). Data could not be pooled for reduction in pruritus scores due to limited studies for each intervention. No serious adverse events were reported across all studies.

Gliricidia sepium (kakawati) is probably as effective and safe as 5% sulfur in the management of patients with scabies and may be a promising alternative herbal treatment. Future RCTs should compare it with scabicides recommended by the Philippine Department of Health and World Health Organization, such as permethrin, benzyl benzoate or oral ivermectin. T. rumphii and S. alata may also be investigated using RCTs that should be adequately powered and with good methodologic quality.

INTRODUCTION: Hydroxychloroquine (HCQ), originally an antimalarial drug, is currently used to treat multiple disorders, especially rheumatic diseases. Given its good efficacy and safety, HCQ is widely administered in pregnant patients. However, the safety profile of HCQ during pregnancy remains controversial due to limited research. In addition, HCQ has been reported to reduce preeclampsia in patients with systemic lupus erythematosus (SLE) and could potentially alleviate the symptom of preeclampsia. However, the clinical profile and molecular mechanism of HCQ in preeclampsia is yet to be fully understood. METHOD: We reviewed the literature on HCQ treatment in pregnancy with rheumatic diseases and preeclamp-sia in PubMed and Web of Science. We also discussed the safety of long-term therapy with HCQ during pregnancy. RESULTS: HCQ mainly modulates autoimmune response through inhibition of lysosomal function, toll-like receptor (TLR) signalling, nicotinamide adenine dinucleotide phosphate-mediated oxidative stress and autophagy. Benefits of HCQ in treating rheumatic diseases, including antiphospholipid syndrome, rheumatoid arthritis and Sjogren's syndrome during pregnancy, has been demonstrated in clinics. In particular, multiple clinical guidelines recommend HCQ as an indispensable therapeutic drug for pregnant patients with SLE. Additionally, it may potentially function in preeclampsia to improve clinical symptoms. CONCLUSION HCQ is effectively used for rheumatic diseases during pregnancy. The benefits of HCQ treatment in rheumatic diseases outweigh the risk of adverse reactions it induces in pregnant women.
Humans ; Hydroxychloroquine/pharmacology* ; Pregnancy ; Female ; Antirheumatic Agents/pharmacology* ; Rheumatic Diseases/drug therapy* ; Pregnancy Complications/drug therapy* ; Pre-Eclampsia/prevention & control* ; Lupus Erythematosus, Systemic/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Antiphospholipid Syndrome/drug therapy* ; Sjogren's Syndrome/drug therapy*

INTRODUCTION: While traditional Chinese medicine (TCM) has a long history and continues to be widely practised, its overall clinical efficacy according to conventional scientific standards remains the topic of ongoing research and exploration. This review focuses on the potential use of acupuncture and Chinese herbal medicine (CHM) in combination with Western medicine in Singapore, based on recently published data on the clinical effectiveness and cost-effectiveness of these TCM treatments. METHOD: We collated and summarised 71 research papers published in the past decade, focusing on randomised controlled trials, systematic reviews and population-based cohort studies that had a total sample size (treatment and control arms) exceeding 60. English-language articles published between 2015 and 2025 were identified by searching PubMed/MEDLINE, the Cochrane Library and the China National Knowledge Infrastructure. The search strategy included intervention terms like "acupuncture", "Chinese medicine", "TCM", "traditional Chinese medicine", "RCT" and "randomized controlled trial"; economic evaluation terms like "cost" and "cost-effectiveness"; and disease conditions of concern. We narrowed our research to the clinical effectiveness and cost-effectiveness of CHM in which either the individual ingredients or the products were listed as Chinese Proprietary Medicines (CPMs). RESULTS: The summary tables demonstrate that the integration of acupuncture and/or CPMs with conventional Western medicine can enhance treatment outcomes across various chronic and non-chronic diseases. Their affordability and preventive focus can contribute to long-term healthcare cost savings, benefiting both patients and the healthcare system as a whole. CONCLUSION With a robust regulatory framework, scientific validation and government support, acupunc-ture and CPMs have an important role in the management of various diseases, especially chronic ones, in Singapore.
Humans ; Singapore ; Medicine, Chinese Traditional/methods* ; Acupuncture Therapy/methods* ; Drugs, Chinese Herbal/economics* ; Cost-Benefit Analysis ; Disease Management

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/metabolism* ; Cell Line, Tumor ; Animals ; Drug Resistance, Neoplasm/genetics* ; Cadherins/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Mutation/genetics* ; Mice, Nude ; Protein Kinase Inhibitors/therapeutic use* ; Cetuximab/pharmacology* ; Afatinib/therapeutic use* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects*

BACKGROUND: Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models. METHODS: Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models. RESULTS: In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids. CONCLUSIONS Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans ; Fibroblasts/drug effects* ; Cellular Senescence/physiology* ; Skin/metabolism* ; Child ; Transcriptome/genetics* ; Aged ; Ultraviolet Rays ; Cells, Cultured ; Galactose/pharmacology*

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

BACKGROUND: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited. Notably, artificial intelligence (AI) technologies have significantly advanced drug discovery. This study aimed to discover RIPK3 inhibitor with AI assistance. METHODS: An acute ocular hypertension model was used to simulate pathological ocular hypertension in vivo . We employed a series of AI methods, including large language and graph neural network models, to identify the target compounds of RIPK3. Subsequently, these target candidates were validated using molecular simulations (molecular docking, absorption, distribution, metabolism, excretion, and toxicity [ADMET] prediction, and molecular dynamics simulations) and biological experiments (Western blotting and fluorescence staining) in vitro and in vivo . RESULTS: AI-driven drug screening techniques have the potential to greatly accelerate drug development. A compound called HG9-91-01, identified using AI methods, exerted neuroprotective effects in acute glaucoma. Our research indicates that all five candidates recommended by AI were able to protect the morphological integrity of RGC cells when exposed to hypoxia and glucose deficiency, and HG9-91-01 showed a higher cell survival rate compared to the other candidates. Furthermore, HG9-91-01 was found to protect the retinal structure and reduce the loss of retinal layers in an acute glaucoma model. It was also observed that the neuroprotective effects of HG9-91-01 were highly correlated with the inhibition of PANoptosis (apoptosis, pyroptosis, and necroptosis). Finally, we found that HG9-91-01 can regulate key proteins related to PANoptosis, indicating that this compound exerts neuroprotective effects in the retina by inhibiting the expression of proteins related to apoptosis, pyroptosis, and necroptosis. CONCLUSION AI-enabled drug discovery revealed that HG9-91-01 could serve as a potential treatment for acute glaucoma.
Animals ; Glaucoma/metabolism* ; Neuroprotective Agents/pharmacology* ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Artificial Intelligence ; Retinal Ganglion Cells/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Male

BACKGROUND: Growing evidence suggests that long non-coding RNAs (lncRNAs) exert pivotal roles in fostering chemoresistance across diverse tumors. Nevertheless, the precise involvement of lncRNAs in modulating chemoresistance within the context of gallbladder cancer (GBC) remains obscure. This study aimed to uncover how lncRNAs regulate chemoresistance in gallbladder cancer, offering potential targets to overcome drug resistance. METHODS: To elucidate the relationship between gemcitabine sensitivity and small nucleolar RNA host gene 1 ( SNHG1 ) expression, we utilized publicly available GBC databases, GBC tissues from Renji Hospital collected between January 2017 and December 2019, as well as GBC cell lines. The assessment of SNHG1, miR-23b-3p, and phosphatase and tensin homolog (PTEN) expression was performed using in situ  hybridization, quantitative real-time polymerase chain reaction, and western blotting. The cell counting kit-8 (CCK-8) assay was used to quantify the cell viability. Furthermore, a GBC xenograft model was employed to evaluate the impact of SNHG1 on the therapeutic efficacy of gemcitabine. Receiver operating characteristic (ROC) curve analyses were executed to assess the specificity and sensitivity of SNHG1. RESULTS: Our analyses revealed an inverse correlation between the lncRNA SNHG1 and gemcitabine resistance across genomics of drug sensitivity in cancer (GDSC) and Gene Expression Omnibus (GEO) datasets, GBC cell lines, and patients. Gain-of-function investigations underscored that SNHG1 heightened the gemcitabine sensitivity of GBC cells in both in vitro and in vivo  settings. Mechanistic explorations illuminated that SNHG1 could activate PTEN -a commonly suppressed tumor suppressor gene in cancers-thereby curbing the development of gemcitabine resistance in GBC cells. Notably, microRNA (miRNA) target prediction algorithms unveiled the presence of miR-23b-3p binding sites within SNHG1 and the 3'-untranslated region (UTR) of PTEN . Moreover, SNHG1 acted as a sponge for miR-23b-3p, competitively binding to the 3'-UTR of PTEN , thereby amplifying PTEN expression and heightening the susceptibility of GBC cells to gemcitabine. CONCLUSION The SNHG1/miR-23b-3p/PTEN axis emerges as a pivotal regulator of gemcitabine sensitivity in GBC cells, holding potential as a promising therapeutic target for managing GBC patients.
Humans ; Deoxycytidine/pharmacology* ; PTEN Phosphohydrolase/genetics* ; Gemcitabine ; RNA, Long Noncoding/metabolism* ; MicroRNAs/genetics* ; Gallbladder Neoplasms/genetics* ; Cell Line, Tumor ; Animals ; Mice ; Drug Resistance, Neoplasm/genetics* ; Mice, Nude ; Antimetabolites, Antineoplastic ; Gene Expression Regulation, Neoplastic