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Study Protocol Open Access
Qingping Deng, Zilian Ye, Xiaotu Xi, Xing Zeng, Qing Liu, Rongyuan Yang
Published online October 23, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00003
Abstract
COVID-19 has resulted in significant long-term sequelae in convalescent patients, impacting overall quality of life. Traditional Chinese medicine (TCM) has shown promise in managing [...] Read more.

COVID-19 has resulted in significant long-term sequelae in convalescent patients, impacting overall quality of life. Traditional Chinese medicine (TCM) has shown promise in managing post-COVID-19 symptoms through syndrome differentiation. This study aimed to evaluate the efficacy and safety of TCM in COVID-19 convalescent patients in a real-world setting.

This prospective, real-world study will be conducted at Guangdong Provincial Hospital of Traditional Chinese Medicine. A total of 528 COVID-19 convalescent patients will be recruited and divided into two groups: a control group receiving routine Western medical treatment and an intervention group receiving additional TCM treatment based on syndrome differentiation. Patients will be assessed for three major TCM syndromes: Lung-Spleen Qi Deficiency, Qi-Yin Deficiency, and Cold Phlegm Obstructing the Lung, with corresponding TCM prescriptions administered accordingly. The primary outcome measure will be the improvement in clinical symptom scores based on a TCM symptom scoring system. Secondary outcomes will include changes in laboratory tests, imaging studies, heart function classification, and quality of life scores. Safety will be assessed through liver and kidney function tests and adverse event monitoring.

The study is expected to demonstrate that TCM treatment, based on syndrome differentiation, can significantly improve clinical symptoms and overall health in COVID-19 convalescent patients compared to routine Western medical treatment. These findings will provide evidence for integrating TCM into post-acute COVID-19 care.

This study will contribute to the evidence supporting TCM as an effective treatment for post-COVID-19 syndrome, enhancing patient outcomes and informing comprehensive recovery strategies.

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Short Communication Open Access
Arsal Khan, Aaron Jaynes, Fatema Ali, Yamini Virkud, Timothy Sun, Isabel O’Connell, Wayne Shreffler, Qian Yuan, Victoria Martin
Published online November 26, 2025
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2025.00026
Abstract
Guaiac fecal occult blood test (gFOBT) is often used to evaluate evidence of food protein-induced allergic proctocolitis (FPIAP) in children in primary care and gastroenterology [...] Read more.

Guaiac fecal occult blood test (gFOBT) is often used to evaluate evidence of food protein-induced allergic proctocolitis (FPIAP) in children in primary care and gastroenterology settings; however, it has not been validated for this diagnosis, and little is known about the positivity rates in early infancy. In this study, we used samples from healthy asymptomatic infants aged two weeks to two months to evaluate the gFOBT positivity rate compared to those diagnosed with FPIAP.

This was a nested case-control study. Frozen stool samples from infants aged two days to five months enrolled in the Gastrointestinal Microbiome and Allergic Proctocolitis study were evaluated using gFOBT (n = 123). The results were interpreted by three blinded staff members, including a trained clinical research coordinator, a pediatric gastroenterologist, and an experienced medical assistant. Additionally, the samples were analyzed using a quantitative fecal immunochemical test (FIT) for hemoglobin to compare with gFOBT results.

Eight percent of samples from the 100 healthy asymptomatic infants were gFOBT positive (11% when including positive and equivocal results). Seventy-four percent of samples from infants diagnosed with FPIAP were gFOBT positive. The interrater reliability of gFOBT interpretation was 81%. Of the healthy samples that yielded a positive gFOBT result, 50% also yielded a positive FIT result. Of the 23 FPIAP samples that yielded a positive gFOBT result, 29% yielded a positive FIT result.

Healthy asymptomatic infants in early infancy were gFOBT positive up to 11% of the time. Caution should be used when interpreting gFOBT results in young infants in a diagnostic setting.

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Original Article Open Access
Telapolu Srivani, Mangathayaru Kalachaveedu, Sugin Lal Jabaris, Cordelia John
Published online June 28, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00013
Abstract
MD-1 is a time-tested polyherbal diabetes supplement in Tamil Nadu, India. It is composed of dried powdered herbs: Phyllanthus amarus Schum. & Thonn, Tinospora cordifolia (Willd.) [...] Read more.

MD-1 is a time-tested polyherbal diabetes supplement in Tamil Nadu, India. It is composed of dried powdered herbs: Phyllanthus amarus Schum. & Thonn, Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms, Emblica officinalis Gaertn., Eugenia jambolana Lam., Gymnema sylvestre R. Br. Ex, and Cassia auriculata Linn. This study aimed to investigate the in vivo effects of MD-1 in high-fat diet (HFD)-induced diabetes mellitus in C57BL/6J mice.

After 10 weeks of HFD induction, diabetic mice (n = 60) were randomized to 21-day treatments with MD-1, metformin, or left untreated on a standard pellet diet. Fasting blood glucose, triacylglycerol (TAG), total cholesterol, and liver tissue markers including superoxide dismutase, glutathione peroxidase, glutathione, thiobarbituric acid reactive substance, glucokinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase expressions were measured. Adipose tissue tumor necrosis factor (TNF)-α infiltration and messenger RNA expression of peroxisome proliferator-activated receptor γ (PPAR-γ) and glucose transporter type 4 (Glut4) were also analyzed.

MD-1 treatment significantly reduced elevated fasting blood glucose, TAG, and total cholesterol in HFD-fed mice and countered HFD-induced weight gain despite unchanged caloric intake. Improved adipose tissue function was evidenced by reduced TNF-α infiltration and increased messenger RNA expression of PPAR-γ and Glut4. MD-1 attenuated HFD-induced fatty liver disease by reducing oxidative stress and TAG accumulation, suggesting a possible two-hit mechanism.

MD-1 administration primarily targets adipose tissue TNF-α signaling in HFD mice, restoring function via PPAR-γ/Glut4 expression. These findings support its glycemic intervention potential and justify its supplementation in diabetes.

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Original Article Open Access
Roa’a Haraka, Raghad Alghamdi, Orjwan Sami Mattar, Arwa Alharthi, Thekra Algasim, Sherooq Haraka, Mohammed Shammas, Muazzam Sheriff Maqbul
Published online November 4, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00034
Abstract
Clove essential oil (CEO) derived from Syzygium aromaticum and miswak (Salvadora persica) contains bioactive compounds with antimicrobial properties. Due to the growing interest [...] Read more.

Clove essential oil (CEO) derived from Syzygium aromaticum and miswak (Salvadora persica) contains bioactive compounds with antimicrobial properties. Due to the growing interest in alternatives to conventional antibiotics, this study aimed to evaluate the in vitro antimicrobial efficacy of CEO, miswak, and their combination against key peri-implantitis pathogens.

The antimicrobial activities of CEO, miswak, and their combinations were tested against Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia. Disc diffusion and serial dilution methods were used to measure the inhibition zones and minimum inhibitory concentrations, respectively. Doxycycline served as a standard antibiotic for comparison, while ethanol was used as a negative control. Data were analyzed using one-way analysis of variance and Tukey’s honestly significant difference test, with significance set at α = 0.05.

CEO exhibited inhibition zones of 10–16 mm, comparable to that of doxycycline (13–16 mm), whereas miswak (6–13 mm vs. 1–14 mm) and the CEO–miswak combination (8–14 mm vs. 0–14 mm) showed lower activity. Mean minimum inhibitory concentration values were lowest for doxycycline (1.73 ± 0.46 µg/mL), followed by CEO (2.37 ± 0.24 µg/mL) and CEO–miswak combination (2.92 ± 0.12 µg/mL). Statistical analysis showed that the CEO–miswak combination was less effective than CEO (p = 0.0326) and doxycycline (p = 0.0001), but not different from miswak (p = 0.9836). CEO showed slightly greater activity than miswak (p = 0.0605).

Among the natural extracts tested, CEO exhibited superior antimicrobial efficacy, whereas miswak was less effective. The combination of CEO with miswak did not enhance antimicrobial efficacy, suggesting antagonistic interactions between their bioactive compounds.

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Original Article Open Access
Nourhan Badwei, Amal Tohamy Abdel Moez, Nashwa El-Khazragy, Mohammed Soliman Gado
Published online September 5, 2025
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Gene Expression. doi:10.14218/GE.2025.00040
Abstract
Circular RNAs (circRNAs) are non-coding RNAs characterized by a strictly closed-loop covalent structure. They are abundantly detected in various cells due to their conserved nature. [...] Read more.

Circular RNAs (circRNAs) are non-coding RNAs characterized by a strictly closed-loop covalent structure. They are abundantly detected in various cells due to their conserved nature. Studies have reported their potential association with chronic liver disease (CLD), including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), with possible roles as diagnostic and prognostic markers. This study aimed to analyze the potential use of serum-derived hsa_circ_101555 as a diagnostic tool for CLD without HCC, and to compare it with other known non-invasive parameters for liver disease severity and inflammation. Additionally, it aimed to evaluate its expression among non-HCC CLD patients, CLD with HCC cases reported in our published (phase I) study, and healthy controls.

A cross-sectional study (phase II) was conducted involving 30 clinically, laboratory, and radiologically diagnosed Egyptian non-HCC CLD patients and 30 healthy subjects. The serum expression level of hsa_circ_101555 was measured using real-time polymerase chain reaction. The diagnostic accuracy was assessed through receiver operating characteristic curve analysis, calculating the area under the curve to determine sensitivity and specificity. The study also compared hsa_circ_101555 levels with established non-invasive parameters such as the Child-Turcotte-Pugh and model for end-stage liver disease scores, as well as inflammatory markers like the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

hsa_circ_101555 demonstrated high diagnostic accuracy (area under the curve of 0.970) at a cutoff point of 2.088 for differentiating non-HCC CLD patients from healthy controls. Elevated circRNA levels were noted in patients with hepatic encephalopathy and ascites, correlating with advanced liver disease scores (Child-Turcotte-Pugh/model for end-stage liver disease scores). Mean circRNA values were highest in HCC cases, followed by non-HCC CLD patients, and lowest in healthy controls.

Serum-derived hsa_circ_101555 demonstrates high diagnostic accuracy in differentiating non-HCC CLD patients from healthy controls. These findings suggest that hsa_circ_101555 has the potential to serve as a reliable non-invasive biomarker for the early diagnosis of CLD, correlating with disease severity and inflammation markers. Further research with larger sample sizes is warranted to validate its clinical utility and enhance the management of CLD.

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Original Article Open Access
Ellen S. Wagner, Kaitlyn Oliphant, Mark D’Souza, Wilfredo Cruz-Ayala, Ruba K. Azzam, Bree Andrews, Erika C. Claud
Published online November 5, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00152
Abstract
Parenteral nutrition (PN)-associated cholestasis (PNAC) is frequently diagnosed in premature infants; however, not all PN-exposed infants develop PNAC. We propose that, in premature [...] Read more.

Parenteral nutrition (PN)-associated cholestasis (PNAC) is frequently diagnosed in premature infants; however, not all PN-exposed infants develop PNAC. We propose that, in premature infants receiving PN and varying amounts of enteral feeds, differences in the gut microbiome and fecal bile acid content are associated with PNAC development. This study aimed to examine the fecal microbiome and bile acid content of premature infants on PN to determine if there is a relationship with the development of PNAC.

Twenty-two preterm infants had serial bilirubin measurements and fecal samples collected during their neonatal intensive care unit admission. Fecal samples underwent 16S rRNA gene sequencing and bile acid analysis. Binomial regression, adjusting for postmenstrual age with feed amount as a moderator, was used to assess the impact of the fecal microbiome and bile acids on PNAC development.

Cholestatic patients (n = 11) had greater PN and antibiotic exposure (p = 0.020; p = 0.010) and longer neonatal intensive care unit stays (p = 0.0038) than non-cholestatic patients. Microbiome richness was higher in non-cholestatic infants (p < 2E-16), with no difference in β diversity (p = 1.0). Cholestatic infants had a significantly higher abundance of Proteobacteria and Fusobacteriota and a lower abundance of Bacteroidota (p < 2E-16). Akkermansia was abundant in all infants on low feeds; as feed volume increased, Akkermansia abundance significantly increased in non-cholestatic infants (p < 2E-16). Bile acid analysis demonstrated significantly lower deoxycholic acid concentrations in cholestatic infants (p < 2E-16). Metagenomic analysis revealed an increase in Proteobacteria requiring augmented stress responses in non-cholestatic infants.

This is the first study to directly explore the relationship between PNAC susceptibility, the microbiome, and fecal bile acids in preterm infants. The microbiome and bile acid patterns identified here may inform the development of targeted therapeutics for this vulnerable population.

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Original Article Open Access
Renaud Nonmarmbaye, Alcherif Hamid Mahamat, Sidiki Neteydji, Fadoul Mahamat Fadoul, Touo’yem Nkemmo Willy Stéphane, Elisabeth Ngo Bum
Published online September 1, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00039
Abstract
Sclerocarya birrea (A. Rich) Hochst (Anacardiaceae) is a plant widely used by traditional healers in several African countries to treat numerous illnesses such as Alzheimer’s disease, [...] Read more.

Sclerocarya birrea (A. Rich) Hochst (Anacardiaceae) is a plant widely used by traditional healers in several African countries to treat numerous illnesses such as Alzheimer’s disease, schizophrenia, inflammation, infections, arterial hypertension, headaches, and others. This study aimed to determine the therapeutic efficacy of Sclerocarya birrea (S. birrea) against glutamate-induced neurotoxicity.

Thirty naïve white mice (Mus musculus Swiss, Muridae), of both genders and weighing between 18 and 25 g, were used in the experiments. Different doses (102.5, 205, and 410 mg/kg) of the extract and vitamin C (100 mg/kg) were administered to the animals one hour before administration of monosodium glutamate (4 mg/kg) for 15 consecutive days. T-maze and Y-maze tests were conducted over three days to assess the animals’ behavioral performance. After behavioral testing, the animals were sacrificed and their brains removed for analysis of oxidative stress parameters.

S. birrea extract reversed glutamate-induced behavioral alterations by significantly (P < 0.001) reducing the latency to reach the platform in the T-maze and significantly increasing the percentage of spontaneous alternation in the Y-maze. The extract also significantly counteracted (P < 0.001) glutamate-induced oxidative stress parameters. The 102.5 and 205 mg/kg doses of the extract significantly (P < 0.001) reduced catalase and reduced glutathione levels, as well as the increase in malondialdehyde levels induced by glutamate.

S. birrea root bark extract exhibits neuroprotective properties that facilitate memory and ameliorate glutamate-induced cognitive deficits in white mice. The results provide partial justification for the traditional medicinal use of S. birrea extract.

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Review Article Open Access
WenQing Yang
Published online December 9, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00045
Abstract
The association between chronic inflammation and cancer has reshaped our understanding of tumorigenesis and cancer therapy. Inflammatory responses can both promote and suppress [...] Read more.

The association between chronic inflammation and cancer has reshaped our understanding of tumorigenesis and cancer therapy. Inflammatory responses can both promote and suppress cancer, depending on the context and timing. Key molecular players, such as nuclear factor kappa-light-chain-enhancer of activated B cells, interleukin-6, signal transducer and activator of transcription 3, and a variety of immune cell types, including tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, orchestrate an environment conducive to tumor survival, angiogenesis, metastasis, and immune evasion. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. However, its success varies across tumor types and patients, underscoring the need to understand the tumor microenvironment and inflammatory context. This review examines the mechanistic underpinnings of inflammation-driven cancer, discusses translational research efforts targeting inflammatory pathways, and explores clinical applications, including the integration of immunotherapy with anti-inflammatory agents and biomarkers for personalized treatment. Future directions in the field include the application of artificial intelligence, microbiome research, single-cell technologies, and gene editing tools to further tailor therapies and overcome resistance mechanisms.

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Original Article Open Access
Samuel T. Adeleke, Christopher Igbeneghu
Published online July 31, 2025
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00014
Abstract
Metaplastic breast carcinoma, a rare entity (<1% of breast neoplasms), lacks comprehensive spectroscopic characterization. This study aimed to address this gap by providing a [...] Read more.

Metaplastic breast carcinoma, a rare entity (<1% of breast neoplasms), lacks comprehensive spectroscopic characterization. This study aimed to address this gap by providing a qualitative and quantitative spectroscopic profile of metaplastic carcinoma in comparison to ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC).

A retrospective analysis was conducted on archival tissue blocks of metaplastic carcinoma (n = 10), DCIS (n = 12), and IDC (n = 31). Sections were stained with hematoxylin and eosin for histological confirmation. Attenuated total reflectance Fourier-transform infrared spectroscopy was performed on adjacent unstained sections, with normal breast tissue (n = 10) serving as the control. Spectral data were analyzed using t-tests to identify significant differences in peak intensities and ratios. Hierarchical clustering analysis and receiver operating characteristic curves were generated to assess the diagnostic potential of selected spectral features.

Spectral analysis revealed that mean peak intensities were generally lower in all carcinoma subtypes compared to normal breast tissue. Specific ratios, including A1237/A1080 (phosphate; p < 0.01), A1043/1543 (glycogen; p < 0.01), and A1080/A1632 (nucleocytoplasmic index; p < 0.03), were significantly elevated in carcinomatous tissues. Receiver operating characteristic analysis identified peak 3,280 (area under the curve (AUC) = 0.93–0.96) as highly effective in differentiating normal from carcinomatous tissues. Peak 2,922 showed specificity for distinguishing normal tissue from IDC (AUC ≈ 0.7). Peak 1,744 effectively discriminated between DCIS and metaplastic carcinoma (AUC = 0.7). The ratio 1,080/1,632 (nucleocytoplasmic ratio) demonstrated exceptional diagnostic accuracy, distinguishing normal from carcinomatous tissues (AUC ≈ 1.0), DCIS from IDC (AUC ≈ 0.86), and DCIS from metaplastic carcinoma (AUC ≈ 0.8).

Attenuated total reflectance Fourier-transform infrared spectroscopy, particularly using peak 3,280 (Amide A) and the 1,080/1,632 ratio (nucleocytoplasmic index), offers a promising approach for discriminating between normal breast tissue and carcinoma, as well as differentiating pre-IDC from metaplastic carcinoma. These spectral markers demonstrate both statistical significance and diagnostic potential.

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Letter to the Editor Open Access
Mengqin Guo, Yang Liu, Jiezuan Cen, Chuanbin Wu, Zhengwei Huang
Published online August 21, 2025
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00028
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