Category Archives: b_original_articles

Jingyu Feng^1,2, Li Yang¹, Jiguo Wang^1,2, Jing Zhang^1,2, Lizhu Lin^2,3*

¹Department of Oncology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Shenzhen 518133, China

²The First School of Clinical Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, Guangdong, China

³Department of Oncology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, Guangdong, China

Abstract

The objective of this study was to elucidate the mechanism of the Hexuetongbi formula in treating Chemotherapy-induced Peripheral Neuropathy (CIPN) using network pharmacology, pharmacodynamics, and mechanistic approaches in an oxaliplatin-induced peripheral neuropathy rat model. Network pharmacology is crucial for understanding the multi-target effects of the Hexuetongbi formula on CIPN. This approach allows for a comprehensive mapping of the complex interactions between the formula’s constituents and the biological pathways involved in CIPN, revealing potential synergistic effects and enhancing the formula’s pharmacological validation. The Hexue Tongbi formula’s impact was analyzed on rats undergoing peripheral neuropathy, observing changes in the morphology of L4-6 dorsal root ganglion neurons through hematoxylin and eosin (HE) staining. Simultaneously, a network pharmacology approach was employed, utilizing TCMSP and GeneCards databases to identify common targets between CIPN and Hexue Tongbi’s therapeutic entities. These core targets were scrutinized through GO enrichment and KEGG pathway analysis. To validate the findings, mRNA and protein expression levels in the L4-6 dorsal root ganglion were examined using quantitative PCR and Western Blot assays. Significant modifications were observed in the frequency of cold stimulus withdrawal reflexes and the L4-6 dorsal root ganglion neurons, while the mechanical withdrawal reflex threshold displayed a considerable decrease. In rats treated with the Hexuetongbi formula post-oxaliplatin, there was noteworthy mitigation in the cold stimulation paw withdrawal threshold and augmentation in the mechanical stimulation paw withdrawal threshold. Network pharmacology identified 19 active constituents in Hexuetongbi and 35 targets for CIPN, with the PI3K/Akt signaling pathway emerging as a prominent target. There was a significant upregulation in PI3K, Akt1, Akt2, and Bcl-2 compared to controls, suggesting that Hexuetongbi effectively mitigates oxaliplatin-induced peripheral neuropathy through the modulation of the PI3K/Akt and Bcl-2 pathways.

Keywords: Oxaliplatin, Chemotherapy-induced peripheral neuropathy, Traditional Chinese medicine, Dorsal root ganglion, Apoptosis

Xinyou Liu^2,3, Yihong Luo¹, Zhenglin Wang¹, Cong Wang^1,2,3*

¹Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

²Department of General Surgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, China

³Xiamen Clinical Research Center for Cancer Therapy, Xiamen 361015, China

Abstract

This study addresses a critical knowledge gap in understanding the tumor microenvironment of thyroid cancer by elucidating the mechanism by which tumor cell-derived CD133-positive exosomes promote lymph node metastasis. We employed molecular docking, western blot, and other molecular characterizations to investigate the crucial interaction between CD133 and VEGFR3 and its impact on metastasis. Additionally, experiments assessed the influence of CD133-positive exosomes on lymphatic endothelial cell proliferation and migration.

Our findings demonstrate a significant direct interaction between CD133 and VEGFR3, as suggested by molecular docking. Furthermore, inhibition of CD133 expression resulted in a notable reduction in lymph node metastasis. We also observed that CD133-positive exosomes derived from thyroid cancer cells actively contribute to the migration and proliferation of lymphatic endothelial cells.

These results unveil a novel pathway for lymph node metastasis in thyroid cancer. The identification of CD133 and its interaction with VEGFR3 as key players in this process holds significant promise for the development of targeted therapeutic strategies.  By focusing on these targets, researchers can potentially improve the prognosis of patients with thyroid cancer.

Keywords: Thyroid cancer cells, Exomes, Lymph node metastasis, CD133, VEGFR3

Edith L. Kadege^1*, Pavithravani B. Venkataramana¹, Teshale Assefa², Joseph C. Ndunguru³, Jean Claude Rubyogo⁴, Ernest R. Mbega¹

¹School of Life Sciences and Bioengineering, The Nelson Mandela African Institution of Science and Technology, Arusha 447, Tanzania

²Crops for Nutrition and Health, International Center for Tropical Agriculture (CIAT), 2704 Arusha, Tanzania

³Department of Research and Innovation, Tanzania Agricultural Research Institute (TARI), Dodoma 1571, Tanzania
⁴Crops for Nutrition and Health, International Center for Tropical Agriculture (CIAT), Nairobi 823-00621, Kenya

Abstract

Tanzania is the top bean producer in Africa and seventh globally, exporting half of its beans to neighboring nations. This study determines common bean varietal performance in northern Tanzania. Disease infection and yield components of 22 genotypes were evaluated in on-station and on-farm trials. The study used a completely randomized factorial trial design with three replications to explore the individual and combined effects of genotype and environment on disease infection and grain yield in two on-station and six on-farm environments. Data were collected on number of emerging plants; canopy height, canopy width, plant vigor, disease infection levels, plant stands at harvest, number of pods per plant, number of grains per pod, 100-grain weight and grain yield and analyzed using R software. The combined analysis of variance revealed significant differences among genotypes, environment, and genotype by environment interactions. Bean canopy height, canopy width, plant vigor and grain yield were high at on-station trials, compared with on-farm trials. Advanced breeding lines showed 56% higher grain yield than commercial checks across study locations. Additive main effects and multiplicative interaction (AMMI) analysis revealed that, genotype was the dominant factor affecting common bean grain yields at 50.3%, whereas the environmental impacts were 25.7%. NUA 48 and NUA 64 were ideal genotypes showing anthracnose resistance and delivering higher grain yield. VTT 923-23-10 and Sweet Violet varieties were stable across the mega-environment. Therefore, NUA 48, NUA 64, VTT 923-23-10 and Sweet Violet are proposed for further evaluation within Tanzanian bean agroecosystem to identify farmers’ preferred varieties.

Keywords: Disease resistance, Yield components, Breeding lines, Bean, Tanzania

Sara Bano¹, Muhammad Imtiaz Rashid², Amna Akhtar¹, Farhan Hafeez¹, Rashid Nazir¹, Faridullah¹, Muhammad Irshad¹, Gabrijel Ondrasek^3*, Akhtar Iqbal^1*

¹Department of Environmental Sciences, COMSATS University Islamabad (CUI), Abbottabad Campus, Tobe Camp, University Road, Abbottabad, Pakistan.

²Center of Excellence in Environmental Studies, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

³Department of Soil Amelioration, Faculty of Agriculture, University of Zagreb, HR-10000 Zagreb, Croatia.

Abstract

To enhance soil fertility and subsequent crop yields, digestate, byproduct of anaerobic digestion, can serve as a supplement or potential alternative to chemical fertilizers when sensibly utilized. This study assessed the impact of two types of digestates on two distinct soils for the perspective of agriculture (affecting pH, EC, organic carbon and mineral nitrogen) and environment (mineral nitrogen leaching under two rainfall patterns). Both soils mainly differed in silt and sand contents: 32% silt and 47% sand for soil-1 and 42% silt and 39% sand for soil-2. Two sets of controlled experiments served the purpose, in which first set involved a soil incubation experiment, applying two digestates to two soil types at 28°C for 60 days. The second set comprised reconstituted soil columns to collect soil solutions at depths of 2.5 cm and 7.5 cm after rainfall application under two patterns for 45 days. Results indicated that application of both digestates in test soils initially increased pH at day 15, followed by a decrease at days 30 and 60. Both digestates significantly elevated soil electrical conductivity compared to control treatments in both soils. Organic carbon content displayed variable impacts, with a slight decrease for solid digestate (12%) and higher decrease for liquid-amended soil (43%) for soil-1. While a significant decrease was observed for soil-2 throughout the incubation period for both amendments (34% and 36% for solid and liquid amended soils respectively). Rapid nitrification occurred with the application of both digestates in both soils, albeit at different rates. Soil-2 exhibited 1.2 to 2 folds higher net nitrification rate (depending upon digestate type and days of incubation) compared to soil-1. Liquid digestate induced more mineral nitrogen compared to solid digestate in both soils. Interestingly, rainfall frequency, digestate type, and soil type influenced the leaching of ammonium and nitrates, with nitrates recording higher levels in both soils, at both depths, and under both rainfall patterns.

 Keywords: Slurry, Nitrates, Crop productivity, Nitrification rate, Soil nutrition

Runglawan Sudmoon¹, Arunrat Chaveerach², Unchaleeporn Ameamsri², Penkhae Thamsenanupap^3,4, Natapol Pumipuntu^4,5, Shiou Yih Lee⁶, Ong Ghim Hock⁶, Tawatchai Tanee^3,4*

¹Faculty of Law, Khon Kaen University, Khon Kaen, Thailand

²Department of Biology, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand

³Faculty of Environment and Resource Studies, Mahasarakham University, Maha Sarakham, Thailand

⁴One Health Research Unit, Mahasarakham University, Maha Sarakham, Thailand

⁵Faculty of Veterinary Sciences, Mahasarakham University, Maha Sarakham, Thailand

⁶Faculty of Health and Life Sciences, INTI International University, Negeri Sembilan, Malaysia

Abstract

Heavy metal contamination, notably lead (Pb), poses a threat to plants and, consequently, human health through the food chain. This study investigates Pb accumulation in rice and how it affects the rice DNA. The rice (Oryza sativa) samples were cultivated in the soil supplemented with Pb at concentrations of 0, 15, 30, 60, and 120 mg/kg. Then the samples were harvested and analyzed for Pb accumulation and DNA alterations using the PCR amplification profiles measured through genomic template stability (GTS). The results demonstrate a Pb concentration hierarchy (root > stem > leaves), with Bioconcentration Factor (BCF) and Translocation Factor (TF) rising when soil Pb contents are supplemented. For DNA alterations, observed GTS values ranged from 23.3 to 76.67%, revealed a general decline with increasing Pb. This correlation assured the influence of Pb on rice DNA stability. Our findings suggest that heavy metal concentration, particularly Pb, has a direct influence on the integrity of rice DNA. Understanding these dynamics is vital for unraveling the complexities of heavy metal-induced genetic changes in plants and their potential implications for food safety and environmental health.

Keywords: Bioconcentration Factor, DNA changes, Genomic template stability, Lead accumulation, Translocation Factor

Rabia Kalsoom1, Hani Z. Asfour2, Hafiz Muhammad Ali3, Abdul Qayyum3*, Shazia Anjum4**, Faisal Maqbool1, Nuzhat Sial1, Riaz Hussain3, Sultan H. Alamri5, Nadeem Ali6, Nisreen Rajeh7, Irfan Irshad8, Asif Idrees9
1Department of Zoology, The Islamia University of Bahawalpur, 63100, Pakistan
2Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah-21589, Saudi Arabia
3Faculty of Veterinary and Animal Sciences, The Islamia University of Bahawalpur, 63100, Pakistan
4Faculty of Chemical and Biological Sciences, The Islamia University of Bahawalpur, 63100, Pakistan
5Department of Family Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah-21589, Saudi Arabia
6Center of Excellence in Environmental Studies, King Abdulaziz University, Jeddah-21589, Saudi Arabia
7Department of Clinical Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah-21589, Saudi Arabia
8Institute of Continuing Education and Extension, University of Veterinary and Animal Sciences, Lahore-54000, Pakistan
9KBCMA, College of Veterinary and Animal Sciences, Narowal, Pakistan

Abstract

Currently terrestrial ecologies are polluted by numerous chemical compounds unceasingly leading to high risk of exposure to variety of life. Among these, bifenthrin is widely used for the control of different sucking and chewing insects and other leaf miner insects around the globe. The current study elaborated the toxic effects of oral administration of bifenthrin in male Japanese quails at sub-lethal (less than 1% mortality) concentrations (10mg/kg, 20mg/kg and 30mg/kg b.w.) during a period of 30 days. During the course of the study, the quails did not show any behavioural or clinical signs. However, a significantly (p<0.05) decreased RBCs and platelets counts and haemoglobin concentration while a significantly (p<0.05) increased MCV, MCHC, total leucocytes and neutrophils were observed in the birds administered with higher concentrations of bifenthrin. Moreover, the incidence of lobed nuclei, blebbed nuclei, condensed nuclei, notched nuclei, binuclear, pear shaped and micro-nuclei were significantly (p<0.05) increased in the erythrocytes of the groups C and D during the experiment. The diameter of seminiferous tubules, height of germinal epithelium and the number of seminiferous tubules containing normal spermatozoa were significantly (p<0.01) decreased while the number of pyknotic cells and degenerated seminiferous tubules were increased significantly (p<0.05) towards the end of the experiment (day-30) in the quails of groups C and D compared to the control group. Hence, the alterations in the hematological indices and histopathological changes in heart, spleen and testes indicate potential toxicity of bifenthrin and its adverse effects in the Japanese quail even at sub-lethal concentrations.

 Keywords: Bifenthrin, Blood profile, Nuclear alterations, Seminiferous tubules, Histo-pathology, Testes

Mahmood Rasool^1*, Khalid I Alhassan², Sajjad Karim¹, Absarul Haque³, Mohammed HZ Mutwakil², Mohammed Alharthi⁴, Adeel G Chaudhary¹, Peter Natesan Pushparaj¹

¹Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

²Department of Biological Science, King Abdulaziz University, Jeddah, Saudi Arabia

³King Fahd Medical Research Center, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

⁴Faculty of Medicine, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia

Abstract

Despite considerable advancements in research, particularly in oncology, colorectal cancer (CRC) remains a formidable and deadly disease. It is crucial to delve deeper into the effects of targeted therapies, signaling pathways, and genetic regulation to ensure the effectiveness of cancer treatments. In this study, we obtained microarray data for four patient-derived CRC organoids from the Gene Expression Omnibus (GEO) database (accession number: GSE114060). We then used several next-generation knowledge discovery (NGKD) tools, such as GEO2R, Metascape, WebGestalt, and Ingenuity Pathway Analysis (IPA) software, to investigate the underlying molecular mechanisms in colorectal cancer-derived organoids treated with trametinib compared to those treated with DMSO. Our NGKD analysis revealed upregulation of SAMD, TP53, and SPTLC3 and downregulation of SPRED1, TGFBI, and DUSP6. The MAPK/ERK signaling pathway was significantly downregulated and was associated with reduced expression of CDX2 in CRC organoids treated with trametinib. We concluded that SAMD9, SPRED1, TGFBI, TP53, and DUSP6 are differentially regulated and can play a pivotal role in the downregulation of the MAPK/ERK signaling pathway to suppress CRC. The use of targeted therapies to regulate the specific gene signatures identified in the current study may be beneficial in the CRC associated tumor suppression . On the other hand, upregulation of SPTLC3 may be induced by MEK inhibitors and may cause hepatotoxicity alongside nonalcoholic steatohepatitis.

Keywords: Colorectal cancer, Organoids, Tumor suppression, MAPK/ERK signaling pathway, MEK inhibitor, Hepatotoxicity

Narumon Tangthirasunun^1*, Darbhe Jayarama Bhat^2,3 , Supattra Poeaim¹

¹Department of Biology, School of Science, King Mongkut’s Institute of Technology Ladkrabang, Bangkok, 10520, Thailand

²Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

³Vishnugupta Vishwavidyapeetam, Ashoke, Gokarna, 581326, India

Abstract

Twenty-seven coprophilous fungi, isolated from field-fed cow dung in an organic farm in Thailand, were identified using morphology and ITS barcode. A total of five genera viz. Aspergillus, Hamigera, Paecilomyces, Penicillium, and Talaromyces were identified with varying numbers and growth rates. These fungi were evaluated for their antibacterial properties against Gram-positive (Bacillus subtilis, Kocuria rhizophila, Staphylococcus aureus and St. epidermidis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. Pe. javanicum NTD-SP2-01 and Talaromyces sp. NTD-SP5-48 exhibited activity against all bacteria when tested with agar plug diffusion method. Talaromyces sp. NTD-SP5-48 was particularly effective against Gram-negative bacteria. As. terreus NTD-NG1-05 displayed the highest activity against five bacterial strains, except Ps. aeruginosa. Notably, As. terreus NTD-NG1-05 and Talaromyces sp. NTD-SP5-48 demonstrated extended antibacterial activity in the agar disk diffusion method, with fermented broth (FB) showing superior inhibitory effects compared to mycelial extract (MY). Both isolates demonstrated significant antibacterial activity against B. Subtilis. Furthermore, all isolates exhibited significant antibacterial activity against B. subtilis, with a diffusion of 0.125 mg/disk. Only Talaromyces sp. NTD-SP5-48 (FB) displayed the highest inhibition activity against Ps. aeruginosa, with a diffusion of 1 mg/disk (100 mg/mL). In terms of enzyme activity, all isolates exhibited cellulase activity, with Talaromyces sp. showing the highest cellulase activity, followed by As. terreus. Laccase activity was only observed in the unidentified isolate NTD-SP5-34, while none of the isolates showed pectinase activity.

Keywords: Antimicrobial activity, Coprophilous fungi, Heat-resistant fungi, Lignocellulolytic enzymes

Masood Ur Rehman¹, Syed Muhammad Suhail¹, Iqbal Munir², Rajwali Khan^1*

¹Department of Livestock Management, Breeding and Genetics, The University of Agriculture, Peshawar, 25130, Khyber Pakhtunkhwa, Pakistan

²Institute of Biotechnology and Genetic Engineering, The University of Agriculture, Peshawar, 25130, Khyber Pakhtunkhwa, Pakistan

Abstract

The current study aimed to evaluate the impact of three different agroecological zones on the productive and reproductive performance of Holstein-Friesian (HF) cows, along with their comparative analysis of physiological and molecular markers under subtropical conditions of Pakistan. The productive (milk yield and composition) and reproductive (service per conception and calving interval) performance of genetically identical (n=210) HF cows placed across three agroecological zones: irrigated lowlands (Okara), wet (Abbottabad), and dry (Queta) highlands were analyzed. Additionally, heat stress markers (superoxide dismutase, glutathione peroxidase, serum cortisol, bovine heat shock protein 70 (HSP-70), and blood glucose) from five cows in each location (n=15 in total) were also investigated in early and late summers using commercial ELISA and calorimetric kits. Furthermore, the mRNA levels of heat shock protein genes HSPA8 and HSP90AB1 were also quantified in three agroecological zones through qRT-PCR.  The results revealed that cows raised in the wet highlands of Abbottabad exhibited significantly higher (P<0.05) milk production (daily and total lactational yield), and the lowest service period, calving interval and number of services per conception as compared to the cows from the other two agroecological zones. Furthermore, there was a significant effect (P<0.05) of agroecological zones on the heat stress indicators (SOD, GPX, cortisol, blood glucose, and HSP70) profiles and expression of heat shock protein genes in HF cows. The dairy cows from Abbottabad (Wet highlands) showed a significantly lower profile of heat stress indicators as compared to the cows from the other two agroecological zones. It can be inferred that HF cows function better in moderate agroecological zones of subtropical countries.

Keywords: Heat stress indicators, Subtropics, Holstein-Friesian cows, Agroecological zone

Heer Baloch¹, Irfan Ali Sabir², Saadullah Khan Leghari¹, Muhammad Sohail Saddiq^3*, Pravej Alam⁴, Shahbaz Khan^5*, Esha Mehik Fatima⁶, Mateen Sajid⁷, Muhammad Hammad Raza⁸, Muhammad Arif Hussain¹, Muhammad Ayoub¹, Rashid Iqbal^9,10

¹Department of Botany, Ghazi University, Dera Ghazi Khan, Pakistan

²College of Horticulture, South China Agricultural University, Guangzhou, 510642, China

³Department of Agronomy, Ghazi University, Dera Ghazi Khan, Pakistan

⁴Department of Biology, College of Sciences and Humanities, Prince Sattam Bin Abdulaziz University, Al- Kharj 11942, Saudi Arabia

⁵Colorado Water Center, Colorado State University, Fort Collins, CO, USA

⁶Department of Entomology, Muhammad Nawaz Shareef University of Agriculture, Multan, Pakistan

⁷Department of Horticulture, Ghazi University, Dera Ghazi Khan, Pakistan

⁸Department of Agri. Extension and Education, Ghazi University, Dera Ghazi Khan, Pakistan

⁹Department of Agronomy, Faculty of Agriculture and Environment, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan

¹⁰Department of Life Sciences, Western Caspian University, Baku, Azerbaijan

Abstract

Moringa leaf extract (MLE) as a biostimulant has demonstrated success in boosting the productivity of several agronomic crops, but its impact on Buckwheat crops remains unexplored. Buckwheat, recognized as an essential nutritional and functional food crop, often exhibits lower yields compared to major cereal crops grown in similar environments. Therefore, this research aimed to investigate the impact of different concentrations (1%, 2%, and 3%) of MLE on the agricultural performance of common buckwheat (CB) and tartary buckwheat (TB). A pot experiment was carried out according to completely randomized design with factorial arrangements having three replications. Results demonstrated significant improvements in growth parameters (branches, leaves, nodes, and internodes) for MLE-treated plants compared to the control group. Foliar treatment MLE 2% also increased chlorophyll content, improved membrane stability index (MSI) and relative water content (RWC), and enhanced biochemical composition (phenolic compounds, free amino acids, leaf proline, and soluble sugars) in both buckwheat genotypes followed by MLE 3% and MLE 1%. TB produced significantly higher grain yield (0.74 g) as compared to CB (0.43 g). The findings showed that a foliar treatment of MLE 2% led to increased grain yield in both TB (0.97 g) and CB (0.55 g) as compared to control group plants (0.37g TB and 0.22 g CB) respectively. This increase was associated with elevated activities of photosynthetic pigments, phenolic content, RWC, free amino acids, soluble sugars, and catalase in both buckwheat genotypes. In conclusion, MLE application at 2% significantly boosted the agriculture performance of buckwheat, and this study unlocked new insights into optimizing the productivity of the vital food crop.

Keywords: Biostimulant, Free amino acid, Phenolic, Buckwheat, Foliar application, Grain yield