Review of Herbal Medicinal Plants Used in the Management of Cancers in the East Africa Region from 2019 to 2023.

BACKGROUND: In the East African region, herbal plants are essential in the treatment and control of cancer. Given the diverse ecological and cultural makeup of the regional states, it is likely that different ethnic groups will use the same or different plants for the same or different diseases. However, since 2019, this has not been compiled into a single study. PURPOSE: The study aimed to compile and record the medicinal plants utilized in East Africa from April 2019 to June 2023 to treat various cancer types. MATERIALS AND METHODS: The study examined 13 original studies that included ethnobotanical research conducted in East Africa. They were retrieved from several internet databases, including Google Scholar, Scopus, PubMed/Medline, Science Direct, and Research for Life. The study retrieved databases on plant families and species, plant parts used, preparation methods and routes of administration, and the country where the ethnobotanical field surveys were conducted. Graphs were produced using the GraphPad Prism 8.125 program (GraphPad Software, Inc., San Diego, CA). Tables and figures were used to present the data, which had been condensed into percentages and frequencies. RESULTS: A total of 105 different plant species from 45 different plant families were identified, including Asteraceae (14), Euphorbiaceae (12), Musaceae (8), and Apocynaceae (7). Uganda registered the highest proportion (46% of the medicinal plants used). The most commonly mentioned medicinal plant species in cancer management was Prunus africana. Herbs (32%), trees and shrubs (28%), and leaves (45%) constituted the majority of herbal remedies. Most herbal remedies were prepared by boiling (decoction) and taken orally (57%). CONCLUSION: East Africa is home to a wide variety of medicinal plant species that local populations and herbalists, or TMP, frequently use in the treatment of various types of cancer. The most frequently used families are Asteraceae and Euphorbiaceae, with the majority of species being found in Uganda. The most frequently utilized plant species is Prunus africana. Studies on the effectiveness of Prunus africana against other malignancies besides prostate cancer are required.

Medicinal plants used in the management of cancers by residents in the Elgon Sub-Region, Uganda.

BACKGROUND: In Uganda, medicinal plants have been utilized to treat a variety of ailments, including cancer. However, there is little information available about the medicinal plants used to treat cancer in the Elgon subregion. As a result, the current study documented the plant species used in the management of cancer in the Elgon sub-region. METHODS: Data were gathered by observation, self-administered questionnaires, interview guides, and guided field trips. Analyzing descriptive statistics and creating graphs were done using SPSS (version 21.0) and GraphPad Prism® version 9.0.0, respectively. Well-established formulae were used to calculate quantitative indices. The narratives were interpreted using major theories and hypotheses in ethnobotany. RESULTS: A total of 50 plant species from 36 families were documented, and herbal knowledge was mainly acquired through inheritance. Fabaceae and Asteraceae comprised more plant species used in herbal preparation. Most plants were collected from forest reserves (63%); herbal therapies were made from herbs (45%); and leaves were primarily decocted (43%). The most frequently used plants were Tylosema fassoglensis, Hydnora abyssinica, Azidarachata indica, Prunus Africana, Kigelia africana, Syzygium cumini, Hydnora africana, Rhoicissus tridentata, Albizia coriaria, and Plectranthus cuanneus. All the most commonly used plants exhibited a high preference ranking (60-86%) and reliability level (74.1-93.9%). Generally, the ICF for all the cancers treated by medicinal plants was close to 1 (0.84-0.95). CONCLUSIONS: The ten most commonly utilized plants were favored, dependable, and most important for treating all known cancers. As a result, more investigation is required to determine their phytochemistry, toxicity, and effectiveness in both in vivo and in vitro studies. This could be a cornerstone for the pharmaceutical sector to develop new anticancer medications.

A di-electrophoretic simulation procedure of iron-oxide micro-particle drug attachment system for leukemia treatment using COMSOL software: a potential treatment reference for LMICs.

Background: Leukemia encompasses various subtypes, each with unique characteristics and treatment approaches. The challenge lies in developing targeted therapies that can effectively address the specific genetic mutations or abnormalities associated with each subtype. Some leukemia cases may become resistant to existing treatments over time making them less susceptible to chemotherapy or other standard therapies. Objective: Developing new treatment strategies to overcome resistance is an ongoing challenge particularly in Low and Middle Income Countries (LMICs). Computational studies using COMSOL software could provide an economical, fast and resourceful approach to the treatment of complicated cancers like leukemia. Methods: Using COMSOL Multiphysics software, a continuous flow microfluidic device capable of delivering anti-leukemia drugs to early-stage leukemia cells has been computationally modeled using dielectrophoresis (DEP). Results: The cell size difference enabled the micro-particle drug attachment to the leukemia cells using hydrodynamic focusing from the dielectrophoretic force. This point of care application produced a low voltage from numerically calculated electrical field and flow speed simulations. Conclusion: Therefore, such a dielectrophoretic low voltage application model can be used as a computational treatment reference for early-stage leukemia cells with an approximate size of 5 µm.

Safety and feasibility of autologous adipose-derived stromal vascular fraction in the treatment of keloids: a phase one randomized controlled pilot trial.

INTRODUCTION: Autologous adipose-derived stromal vascular fraction (SVF) has been described to have therapeutic benefits in the treatment of keloids. However, most of the evidence on its efficacy is based on observational studies the majority of which are conducted in high-income countries and yet the highest burden of keloids is in low- and middle-income countries (LMICs). OBJECTIVES: We set out to determine the safety and feasibility of using autologous adipose derived stromal vascular fraction in the treatment of keloids in LMICs. METHODS: In this phase II randomized controlled pilot clinical trial conducted in the Plastic Surgery Unit of Kirruddu National Referral Hospital in Kampala Uganda, 8 patients were assigned a 1:1 ratio to either SVF or triamcinolone acetonide (TAC) arms. In the SVF arm, a median (Inter quartile range) amount of stromal cell infiltration of 2.7×106 (11×106) was administered, while the controls received 10 mg/ml TAC at a ratio of 1:1 TAC to keloid volume. Primary endpoints were adverse event development based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 tool and feasibility assessment based on ≥ 70% recruitment feasibility and ≥ 80% interventional feasibility rates. RESULTS: The participants' mean age was 27.9 (±6.5) years, with a female predilection of 5 (63%). Overall, no adverse events were reported in the SVF arm, while ulceration in a single patient in the TAC arm, which was a grade II adverse event, was reported. Recruitment feasibility of 80% and interventional feasibility with 100% completion were reported. CONCLUSION: Based on our findings, an autologous adipose-derived stromal vascular fraction is feasible and safe for the treatment of keloids in LMICs.

Unique circulating microRNA profiles in epidemic Kaposi's sarcoma.

Background: Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS and is the most common HIV-related malignancy worldwide. The lack of a diagnostic assay to detect latent and early-stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based noninvasive biomarker assay for epidemic KS. Methods: This was a comparative cross-sectional study involving 27 patients with epidemic KS and 27 HIV-positive adults with no prior diagnosis or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA were performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyse the sequencing data. Results: Fifteen out of the 27 epidemic KS-positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV-positive, KS-negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs downregulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS-negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis. Conclusions: This study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection.

Green synthesis and characterization of iron-oxide nanoparticles using Moringa oleifera: a potential protocol for use in low and middle income countries.

OBJECTIVE: Green synthesized iron(III) oxide (Fe3O4) nanoparticles are gaining appeal in targeted drug delivery systems because of their low cost, fast processing and nontoxicity. However, there is no known research work undertaken in the production of green synthesized nano-particles from the Ugandan grown Moringa Oleifera (MO). This study aims at exploring and developing an optimized protocol aimed at producing such nanoparticles from the Ugandan grown Moringa. RESULTS: While reducing ferric chloride solution with Moringa oleifera leaves, Iron oxide nanoparticles (Fe3O4-NPs) were synthesized through an economical and completely green biosynthetic method. The structural properties of these Fe3O4-NPs were investigated by Ultra Violet-visible (UV-Vis) spectrophotometry, X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM). These nanoparticles exhibited UV-visible absorption peaks at 225 nm (nm) for the sixth dilution and 228 nm for the fifth dilution which indicated that the nanoparticles were photosensitive and the SEM study confirmed the spherical nature of these nanoparticles. The total synthesis time was approximately 5 h after drying the moringa leaves, and the average particle size was approximately 16 nm. Such synthesized nanoparticles can potentially be useful for drug delivery, especially in Low and Middle Income Countries (LMICs).

Clinical presentation and outcomes in children with retinoblastoma managed at the Uganda Cancer Institute.

Background: The majority of patients with retinoblastoma, the most common intraocular cancer of childhood, are found in low-and middle-income countries (LMICs), with leukocoria being the most common initial presenting sign and indication for referral. Findings from the current study serve to augment earlier findings on the clinical presentation and outcomes of children with retinoblastoma in Uganda. Methods: This was a retrospective study in which we reviewed records of children admitted with a diagnosis of retinoblastoma at the Uganda Cancer Institute from January 2009 to February 2020. From the electronic database, using admission numbers, files were retrieved. Patient information was recorded in a data extraction tool. Results: A total of 90 retinoblastoma patients were studied, with a mean age at the first Uganda Cancer Institute (UCI) presentation of 36.7 months. There were more males (57.8%) than females, with a male to female ratio of 1.37 : 1. The majority (54.4%) had retinoblastoma treatment prior to UCI admission. The most common presenting symptoms were leukocoria (85.6%), eye reddening (64.4%), and eye swelling (63.3%). At 3 years of follow-up after index admission at UCI, 36.7% of the patients had died, 41.1% were alive, and 22.2% had been lost to follow-up. The median 3-year survival for children with retinoblastoma in our study was 2.18 years. Significant predictors of survival in the multivariate analysis were follow-up duration ( P ¯ < 0.001 ), features of metastatic spread (P = 0.001), history of eye swelling (P = 0.012), and bilateral enucleation (P = 0.011). Conclusions: The majority of children who presented to the Uganda Cancer Institute were referred with advanced retinoblastoma, and there was a high mortality rate. Retinoblastoma management requires a multidisciplinary team that should include paediatric ophthalmologists, paediatric oncologists, ocular oncologists, radiation oncologists, and nurses.

A systematic review of modeling and simulation approaches in designing targeted treatment technologies for Leukemia Cancer in low and middle income countries.

Virtual experimentation is a widely used approach for predicting systems behaviour especially in situations where resources for physical experiments are very limited. For example, targeted treatment inside the human body is particularly challenging, and as such, modeling and simulation is utilised to aid planning before a specific treatment is administered. In such approaches, precise treatment, as it is the case in radiotherapy, is used to administer a maximum dose to the infected regions while minimizing the effect on normal tissue. Complicated cancers such as leukemia present even greater challenges due to their presentation in liquid form and not being localised in one area. As such, science has led to the development of targeted drug delivery, where the infected cells can be specifically targeted anywhere in the body. Despite the great prospects and advances of these modeling and simulation tools in the design and delivery of targeted drugs, their use by Low and Middle Income Countries (LMICs) researchers and clinicians is still very limited. This paper therefore reviews the modeling and simulation approaches for leukemia treatment using nanoparticles as an example for virtual experimentation. A systematic review from various databases was carried out for studies that involved cancer treatment approaches through modeling and simulation with emphasis to data collected from LMICs. Results indicated that whereas there is an increasing trend in the use of modeling and simulation approaches, their uptake in LMICs is still limited. According to the review data collected, there is a clear need to employ these tools as key approaches for the planning of targeted drug treatment approaches.

Mice depleted for Exchange Proteins Directly Activated by cAMP (Epac) exhibit irregular liver regeneration in response to partial hepatectomy.

The exchange proteins directly activated by cAMP 1 and 2 (Epac1 and Epac2) are expressed in a cell specific manner in the liver, but their biological functions in this tissue are poorly understood. The current study was undertaken to begin to determine the potential roles of Epac1 and Epac2 in liver physiology and disease. Male C57BL/6J mice in which expression of Epac1 and/or Epac2 are deleted, were subjected to partial hepatectomy and the regenerating liver was analyzed with regard to lipid accumulation, cell replication and protein expression. In response to partial hepatectomy, deletion of Epac1 and/or Epac2 led to increased hepatocyte proliferation 36 h post surgery, and the transient steatosis observed in wild type mice was virtually absent in mice lacking both Epac1 and Epac2. The expression of the protein cytochrome P4504a14, which is implicated in hepatic steatosis and fibrosis, was substantially reduced upon deletion of Epac1/2, while a number of factors involved in lipid metabolism were significantly decreased. Moreover, the number of Küpffer cells was affected, and Epac2 expression was increased in the liver of wild type mice in response to partial hepatectomy, further supporting a role for these proteins in liver function. This study establishes hepatic phenotypic abnormalities in mice deleted for Epac1/2 for the first time, and introduces Epac1/2 as regulators of hepatocyte proliferation and lipid accumulation in the regenerative process.