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Nanyingi Mark O., Muchemi GM, Samuel M. Thumbi, Ade F, Clayton O. Onyango, G.Kiama S, Bett B.  2017.  Seroepidemiological Survey of Rift Valley Fever Virus in Ruminants in Garissa, Kenya Vector-Borne and Zoonotic Diseases, Volume 17, Number 2, 2017.


Gawriluk, T. R., Simkin, J., Thompson, K.L., Biswas, S., Clare-Salzler, Z., Kimani, J.M., Kiama, S.G., Ezenwa V.O., Smith, M.  2016.  Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals. Nat. Commun. 7:11164 doi: 10.1038/ncomms11164.



Onzago, RO, Kiama SG, Mbaria JM, D.W Gakuya, C.G. Githiji, Rukenya ZM.  2014.  Analgesic activity of aqueous extract of Vernonia hymenolepis (A. Rich) a traditional medicine plant used in Kenya for toothache. The Journal of Phytopharmacology 2013; 2(6): 41-45. Abstractanalgesic_activity_of_aqueous_extract_of_vernonia_hymenolepis.pdf

The main aim of the study was to ascertain the analgesic properties of Vernonia hymenolepis leaves to validate its use for the treatment of toothache. The plant is widely used as a traditional herb by communities in Trans Nzoia County, Kenya for treatment of various infections including toothache. However its efficacy has not been established. Leaves of the plant were collected from Trans Nzoia County, Kenya and identified at University of Nairobi Herbarium. An aqueous extraction of leaves was prepared. Formalin test was carried out using 30 male albino wister mice to determine antinociceptive effect and the painful response at 0 – 10 min (Early) and 15 – 60 min (late phase). Acetylsalicylate at dose of 100 mg/Kg was used as a positive control. The dose significantly (p<0.05) reduced the time spent in pain behavior in both phases hence indicating that the plant posses antinociceptive activity. It’s concluded that Vernonia hymenolepis possesses analgesic property.

Keywords: Vernonia hymenolepis, Analgesic, Anti-inflammatory, Antinociceptive.

Onzago, RO, Kiama SG, Mbaria JM, Gakuya DW, Nduhiu JG.  2014.  Evaluation of antimicrobial activity and toxicity of Vernonia hymenolepis (A. Rich) traditionally used for toothache in Kenya. The Journal of Phytopharmacology 2014; 3(1): 22-28. Abstractevaluation_of_antimicrobial_activity_and_toxicity_of_vernonia_hymenolepis.pdfevaluation_of_antimicrobial_activity_and_toxicity_of_vernonia_hymenolepis.pdf

Aim: The main aim of the study was to ascertain the antimicrobial properties and safety of Vernonia hymenolepis leaves to validate its use in treatment of toothache. Materials and Methods: The Leaves were collected from Trans Nzoia County, shade dried, ground and both organic and water extraction done. Minimum inhibitory concentration against Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 11778, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Candida albicans was done. Cytotoxicity was done using Brine Shrimp lethality test and lethal concentration (LC50) determined using Finney computer program. The Oral Acute Toxicity Testing (ATC method) was performed as per Organization for economic co-operation and development (OECD) guideline. Result and Discussion: The results showed that the aqueous extract had an inhibitory activity against Staphylococcus aureus and had no significant effect on Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus and Candida albicans at concentration of 400 mg/ml. The organic extract had inhibitory effect against Staphylococcus aureus at a dose of 100 mg/ml and against Pseudomonas aeruginosa and Escherichia coli both at a dose of 400 mg/ ml, Bacillus cereus at a dose of 200 mg/ml and Candida albicans at 50 mg/ml. This study has shown that the plant extracts has a moderate Cytotoxicity with the LC50 (μg /ml) of 491.8 (μg /ml) and 481.7 (μg /ml) for water and organic extract respectively. Acute oral toxicity ATC method showed that the plant extracts in both preparations were not toxic even at a high dose of 2000 mg/kg. Conclusion: It’s concluded that Vernonia hymenolepis possesses antimicrobial activity and is not toxic.
Keywords: Vernonia hymenolepis, Antimicrobial activity, Cytotoxicity, In-vitro.

Kavoi, BM, Plendl J, Makanya AN, Ochieng’ S, Kiama SG.  2014.  Effects of anticancer drug docetaxel on the structure and functionof the rabbit olfactory mucosa. Tissue and Cell. Abstract

Docetaxel (DCT) is an anticancer drug which acts by disrupting microtubule dynamics in the highly mitoticcancer cells. Thus, this drug has a potential to affect function and organization of tissues exhibiting highcellular turnover. We investigated, in the rabbit, the effects of a single human equivalent dose (6.26 mg/kg,i.v.) of DCT on the olfactory mucosa (OM) through light and electron microscopy, morphometry, Ki-67immunostaining, TUNEL assay and the buried food test for olfactory sensitivity. On post-exposure days(PED) 5 and 10, there was disarrangement of the normal cell layering in the olfactory epithelium (OE),apoptotic death of cells of the OE, Bowman’s glands and axon bundles, and the presence (including onPED 3) of blood vessels in the bundle cores. A decrease in bundle diameters, olfactory cell densitiesand cilia numbers, which was most significant on PED 10 (49.3%, 63.4% and 50%, respectively), was alsoevident. Surprisingly by PED 15, the OM regained normal morphology. Furthermore, olfactory sensitivitydecreased progressively until PED 10 when olfaction was markedly impaired, and with recovery from theimpairment by PED 15. These observations show that DCT transiently alters the structure and functionof the OM suggesting a high regenerative potential for this tissue.
© 2014 Elsevier Ltd. All rights reserved.

D.W., G, Mbugua PN, B. K, Kiama SG.  2014.  Effect of Supplementation of Moringa oleifera Leaf Meal in Broiler Chicken Feed. International Journal of Poultry Science . 13 (4): 208-213, 2014 Abstracteffect_of_supplementation_of_moringa_oleifera_leaf_mela_in_broiler_chicken_feed.pdf

The purpose of this study was to evaluate the effect of supplementing Moringa oleifera leaf meal
(MOLM) at different levels in broiler chicken. Broiler starter and finisher diets were formulated using raw
materials obtained from local feed manufacturers. MOLM was first analyzed for crude protein and then added
to diets at levels of 0% (T1), 7.5% (T2), 7.5% (T3) (without Methionine and lysine), 15 (T4) and 30% (T5). Two
hundred (200) day old broiler chicks were randomly allocated into the 5 treatment groups with 4 replicates
of 10 birds each and the diets introduced. The feed intake, feed conversion ratio (FCR), weight gain, lipid
profile, abdominal fat pad and feed digestibility were determined. The MOLM crude protein level was 23.33%.
The weight gain was significantly different between the various diets with the highest weight gain being in
T1 at 1464 and the lowest in diet T5 at 500. MOLM supplementation at levels above 7.5% decreased the feed
intake and dry matter digestibility. The abdominal fat pad (AFP) was significantly higher in T1 compared to
T2, T4 and T5. The males had a significantly high levels of High density lipids (HDL) than females in T2, T3
and T4 (p<0.05). The yellow colour of the carcass increased with the increased levels of MOLM. It was
concluded that Moringa oleifera leaf meal (MOLM) was well tolerated and can only be included in the feed
to levels of up to 7.5% as higher levels affected weight gain, feed intake and digestibility. Further studies on
the yellowing of the carcass, its quality and acceptability by consumers is needed.
Key words: Moringa oleifera leaf meal, broiler chicken, feed intake, weight gain, abdominal fat pad, feed

Ochwang’i, DO, Kimwele CN, Oduma JA, Gathumbi PK, Mbaria JM, Kiama SG.  2014.  Medicinal plants used in treatment and management of cancer in Kakamega County, Kenya. Journal of Ethnopharmacology. 151(3, 12 February 2014):1040–1055. Abstract

Ethnopharmacological relevance

Traditional medicine plays a critical role in treatment of chronic debilitating and life threatening conditions and diseases. Cancer is one such condition whose therapeutic intervention is commonly through inexpensive traditional herbal remedies. Increasingly industrialised societies are developing drugs and chemotherapeutics from these traditional herbal plants. Plant biogeography determines the abundance and availability of medicinal plants which in turn determine their use by local communities. The present study was carried out in Kakamega County of Kenya to identify and document medicinal plants used for treatment and management of cancer states by communities living adjacent to Kakamega Tropical rainforest of Kakamega County, Kenya.

Materials and methods

An ethnobotanical survey was done using semi-structured questionnaires administered to 32 randomly selected herbalists from Kakamega County.

Results and discussion

Sixty five (65) plants of 59 genera and 32 families were identified as candidates in therapeutic intervention against cancer states. Most commonly cited plant species were Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Microglossa pyrifolia (Lam.) Kuntze, Harungana madagascariensis Lam. ex poir, Prunus africana (Hook. f.) kalkman, Cyphostemma serpens (A. Rich), Catharanthus roseus (L.) G. Don and Aloe volkensii Engl. The following were documented for the first time; Aeschynomene abyssinica (A. Rich.) Vatke, Synsepalum cerasiferum (welw.) T. D penn., Albizia coriaria Welw. ex Oliv., Aloe volkensii Engl. Bridelia micrantha (Hochst.) Baill, Croton macrostachyus Delile, Cyphostemma serpens (A. Rich), Dicliptera laxata C.B. Clarke, Ekebergia capensis Sparrm., Gardenia volkensii K. schum. ssp. volkensii, Glycine wightii (wight & Arn.), Ocimum gratissimum Suave, Olea hotcsh spp. hochstetteri, Pavetta abyssinica Fresen., Phyllanthus fischeri Pax, Psydrax schimperiana (A. Rich), Rhus vulgaris Meikle, Senna didymobotyra (Fresen.) Irwin and Barneby, Solanecio nandensis (S. Moore) C. Jeffrey, Solanum mauritianum Scop, Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Spermacoce princea (K. Schum.) Verdc., Tabernaemontana stapfiana Britten, Tragia brevipes Pax and Zanthoxylum gilletii (De Wild.) P.G.Waterman. The most frequently used plant parts were fresh or dried leaves and stem barks. Administration to patients was almost exclusively oral, with the exceptions being topical application especially for breast cancer and skin sarcomas.


This study identified diverse medicinal plants used in therapeutic and management intervention against cancer by communities living adjacent to Kakamega Tropical Rainforest. The primary mode of administration was oral.

Kaingu, CK, Mbaria J, Oduma JA, Kiama SG.  2014.  Ethnobotanical study of medicinal plants traditionally used in Tana River County for management of illnesses.. Asian Journal of Complementary and Alternative Medicine 0 2 (0 2 ); 201 4 ; 0 1 - 05. Abstract

Aim of the study: The objective of the study was to identify and document medicinal plants traditionally used by people of Tana River County, Kenya for the management of various ailments. Materials and methods: The study was conducted in March 2012. Information was gathered from 80 traditional practitioners who lived and practiced in Garsen, Itsowe and Ngao Subdivisions of Tana River using semi-structured questionnaires and focused group discussion. Voucher specimen of cited plants were collected and deposited at the university of Nairobi herbarium. Results: A total of 31 plants distributed in 25 families were identified. The most popular plant species were eleven and were used for the management of pneumonia, arthritis, kidney problems, fibroids, typhoid, breast cancer, tooth ache, malaria, diabetis, convulsions, stomach ache, constipation, poisoning, cholera, diarrhea, mastitis, migraine, tonsilitis, ulcers, asthma, high blood pressure, urinary incontinence, body warts, milk letdown and as immune boosters. Conclusion: The use of herbs is still very common amongst Tana River inhabitants and the healers still rely largely on naturally growing plant species in their locality. Furthermore, the documented medicinal plants can be used as a basis for future phytochemical and pharmacological studies. Keywords: medicinal plants, indigenous management of illnesses Tana River.

Nasimolo, J, Kiama SG, Gathumbi PK, Makanya AN, Kagira JM.  2014.  Erythrina abyssinica prevents meningoencephalitis in chronic Trypanosoma brucei brucei mouse model. Metabolic Brain Disease . Abstracterythrina_abyssinica_prevents_meningoe.pdfWebsite

Human African trypanosomiasis is prevalent in Sub-sahara African countries that lie between 14° North and 29° south of the equator. Sixty million people are at risk of infection. Trypanosoma brucei gambesience occurs in West and Central Africa while Trypanosoma brucei rhodesience occurs in East and Southern Africa. The neurological stage of the disease is characterized by neuroinflammation. About 10 % of patients treated with the recommended drug, melarsoprol develop post treatment reactive encephalopathy, which is fatal in 50 % of these patients, thus melarsoprol is fatal in 5 % of all treated patients. This study was aimed at establishing the potential activity of Erythrina abyssinica in reducing neuroinflammation following infection with Trypanosoma brucei brucei. Swiss white mice were divided into ten groups, two control groups and eight infected groups. Infected mice received either methanol or water extract of Erythrina abyssinica at 12.5, 25, 50 or 100 mg/kg body weight. Parasite counts were monitored in peripheral circulation from the third day post infection up to the end of the study. Brains were processed for histology, immunohistochemistry scanning and transmission electron microscopy. Following infection, trypanosomes were observed in circulation 3 days post-infection, with the parasitaemia occurring in waves. In the cerebrum, typical brain pathology of chronic trypanosomiasis was reproduced. This was exhibited as astrocytosis, perivascular cuffing and infiltration of inflammatory cells into the neuropil. However, mice treated with Erythrina abyssinica water extract exhibited significant reduction in perivascular cuffing, lymphocytic infiltration and astrocytosis in the cerebrum. The methanol extract did not have a significant difference compared to the non-treated group. This study provides evidence of anti-inflammatory properties of Erythrina abyssinica and may support its wide use as a medicinal plant by various communities in Kenya.


Ochwang’i, D, Kimwele C, Kiama SG, Rice N.  2013.  Transcriptional regulation of Rat Endothelial Nitric Oxide Promoter in Pulmonary. Abstract

Nitric oxide levels may exert control on the persistence of pulmonary myofibroblasts cells in pulmonary fibrosis. This study examined the regulation of NO levels by transcription factors that influence the endothelial nitric oxide synthase (eNOS3) gene expression. Using a pGL3-Basic vector plasmid DNA, rat and human eNOS3 gene promoters were inserted upstream of a luciferase reporter gene and cloned in competent E. coli cells (DH5α). Transfection assays were performed and the cells treated with potential regulators of eNOS3 gene. Promoter activity of eNOS3 gene was assayed using the Dual Luciferase reporter gene assay. The results indicated that the rat NOS3 promoter was active in the cells with the human NOS3 promoter showing little or no activity.The results demonstrated that transforming growth factor-β ,EGTA and lipopolysaccharide up regulated transcriptional activity while Phorbol 12-myristate 13- acetate, 23187 and S-nitroso-N-acetylpenicillamine, suppressed eNOS3 transcriptional activity. Treatment with Nw-Nitro-L-arginine methyl ester, had no effect on the gene expression. The results of this study demonstrates that high concentrations of Nitric Oxide (NO) inhibit NOS3 gene activity hence an enhanced expression of eNOS in response to pharmacological interventions using some transcriptional factors from these study could provide protection against interstitial pulmonary.

Kaingu, CK, Oduma JA, Mbaria JM, Kiama SG.  2013.  Ethnobotanical Survey of Medicinal Plants Used For the Management of Male Sexual Dysfunction and Infertility in Tana River County, Kenya. Abstract

Sexual dysfunction afflicts 10% of men of all ages, ethnicities and cultural background. In Tana River County a large percentage of reproductive health ailments are managed by traditional healers. Unfortunately, in traditional medicine practice, there is no documentation and information is passed on verbally from generation to generation. The aim of this study therefore was to identify and document plants that are used for the management of male sexual dysfunctions and infertility in Tana River County. An ethno botanical survey was carried out using structured questionnaires. Nineteen plants belonging to 15 genera and 13 families were reportedly used to treat hypoactive sex drive, manage erectile dysfunction/ impotence and treat male infertility. The plant remedies described and documented in this study represent valuable baseline data on indigenous knowledge, upon which further research can be based. Future scientific research into the efficacy and safe use of the herbs could then prove very useful to herbal medicine practitioners and researchers and will contribute immensely towards future conservation efforts of both the plants and the indigenous knowledge.

Kaluwa, CK, Oduma JA, Mbaria JM, Kiama SG.  2013.  Medicinal plants traditionally used for the management of female reproductive health dysfunction in Tana River County, Kenya. Abstract

Reproductive dysfunction is a major health concern amongst the inhabitants of Tana River County. An ethno botanical study was conducted in Garsen, Itsowe and Ngao sub divisions of Tana River County to document the utilization of medicinal plants for the management of female reproductive ailments. The target population was practicing herbalists from Pokomo, Ormo and Giryama communities in the study area. Structured questionnaires and focused group discussions were used to collect data. Forty eight plant species distributed in 40 genera and 29 families were documented as being important for the management of pregnancy related complications, menstrual disorders, infertility, fibroids and as contraceptives. The species most frequently cited by the herbalists were fourteen. Fifty two percent of the plant species were probably being mentioned for the first time as being useful in reproductive health management. In conclusion, Tana River has a pool of TMPs with a wealth of indigenous knowledge that needs to be exploited. The plants used to treat dysmenorrhea for example may be important analgesic agents that need further investigation while those with anti-fertility properties may contain steroidal phyto chemical compounds. Such species therefore need further investigation to establish their efficacy and mechanism of action.

Keywords medicinal plants, female reproductive ailments, Tana River, Kenya

Ochwang’i, D, Kimwele C, Kiama SG, Rice N.  2013.  Transcriptional regulation of Rat Endothelial Nitric Oxide Promoter in Pulmonary Myofibroblasts cells and its implications in Pulmonary Fibrosis. Abstract

Background: Nitric oxide (NO) levels may exert control on the persistence of pulmonary myofibroblast cells in
pulmonary fibrosis.
Objective: This study set out to examine the regulation of NO levels by transcription factors that influence the
expression of the endothelial nitric oxide synthase (eNOS3) gene.
Methods: Using a pGL3-Basic vector plasmid DNA, rat and human eNOS3 gene promoters were inserted upstream of a luciferase reporter gene and cloned in competent E. coli cells (DH5α). Transfection assays were performed and the cells treated with potential regulators of eNOS3 gene. Promoter activity of eNOS3 gene was assayed using the Dual Luciferase reporter gene assay.
Results: The results indicated that the rat NOS3 promoter was active in the cells, with the human NOS3 promoter showing little or no activity. The results demonstrated that transforming growth factor-β, EGTA and
lipopolysaccharide up-regulated transcriptional activity while Phorbol 12-myristate-13-acetate, 23187 and S-nitroso-N-acetylpenicillamine, suppressed eNOS3 transcriptional activity. Treatment with Nw-Nitro-L-arginine methyl ester had no effect on the gene expression.
Discussion: The results of this study demonstrates that high concentrations of NO inhibit NOS3 gene activity, hence an enhanced expression of eNOS in response to pharmacological interventions using some transcriptional factors from these study could provide protection against interstitial pulmonary.
Key words: Nitric oxide, transcription, NOS3 gene promoter, pulmonary fibrosis

A KeSoBAP Publication ©2013.
All rights reserved. ISSN 2303-9841


Gakuya, DW;, Kiama SG;, Mbaria JM;, Mbugua PN;, Gathumbi PK;, Mathiu M.  2012.  The Potential Use Of Moringa Oleifera As Poultry Feed Supplement In Kenya..
Kavoi, BM, Makanya AN, Kiama SG.  2012.  Anticancer drug vinblastine sulphate induces transient morphological changes on the olfactory mucosa of the rabbit.. Abstract2012.anticancer_drug_vinblastine_sulphate_induces_transient_morphological_changes_on_the_olfactory_mucosa_of_the_rabbit..pdf

Vinblastine sulphate (VBS) is an anticancer drug that acts by disrupting microtubule dynamics of highly mitotic tissue cells. The consequences of VBS on the olfactory mucosa (OM), a tissue with high mitotic numbers, are not clearly understood. We used qualitative and quantitative methods to determine the structural changes that may be produced on the rabbit OM by VBS. Following a single dose (0.31 mg/kg) of this drug, the structure of the mucosa was greatly altered on the first 3-5 days. The alteration was characterized by disarrangement of the normal layering of nuclei of the epithelia, degeneration of axonal bundles, occurrence of blood vessels within the bundles, localized death of cells of Bowman's glands and glandular degeneration. Surprisingly on or after day 7 and progressively to day 15 post-exposure, the OM was observed to regenerate and acquire normal morphology, and the vessels disappeared from the bundles. Relative to control values, bundle diameters, olfactory cell densities and cilia numbers decreased to as low as 53.1, 75.2 and 71.4%, respectively, on day 5. Volume density for the bundles, which was 28.6% in controls, decreased to a lowest value of 16.8% on day 5. In contrast, the volume density for the blood vessels was significantly lower in controls (19.9%) than in treated animals at day 2 (25.8%), day 3 (34.3%) and day 5 (31.5%). These findings suggest that the changes induced on the rabbit OM by VBS are transient and that regenerative recovery leads to the restoration of the normal structure of the mucosa.

© 2012 Blackwell Verlag GmbH.
[PubMed - indexed for MEDLINE]

Kavoi, BM, Makanya AN, Plendl J, Kiama SG.  2012.  Morphofunctional adaptations of the olfactory mucosa in postnatally developing rabbits.. Abstract2012_.morphofunctional_adaptations_of_the_olfactory_mucosa_in_postnatally_developing_rabbits..pdf

Rabbits are born blind and deaf and receive unusually limited maternal care. Consequently, their suckling young heavily rely on the olfactory cue for nipple attachment. However, the postnatal morphofunctional adaptations of olfactory mucosa (OM) are not fully elucidated. To clarify on the extent and the pattern of refinement of the OM following birth in the rabbit, morphologic and morphometric analysis of the mucosa were done at neonatal (0-1 days), suckling (2 weeks), weanling (4 weeks), and adult (6-8 months) stages of postnatal development. In all the age groups, the basic components of the OM were present. However, proliferative activity of cells of the mucosal epithelium decreased with increasing age as revealed by Ki-67 immunostaining. Diameters of axon bundles, packing densities of olfactory cells, and cilia numbers per olfactory cell knob increased progressively with age being 5.5, 2.1, and 2.6 times, respectively, in the adult as compared with the neonate. Volume fraction values for the bundles increased by 5.3% from birth to suckling age and by 7.4% from weaning to adulthood and the bundle cores were infiltrated with blood capillaries in all ages except in the adult where such vessels were lacking. The pattern of cilia projection from olfactory cell knobs also showed age-related variations, that is, arose as a tuft from the tips of the knobs in neonates and sucklings and in a radial pattern from the knob bases in weanlings and adults. These morphological changes may be attributed to the high olfactory functional demand associated with postnatal development in the rabbit.

Copyright © 2012 Wiley Periodicals, Inc.

Seifert, AW, Kiama SG, Seifert MG, Goheen JR, Palmer TM, Maden M.  2012.  Skin shedding and tissue regeneration in African spiny mice (Acomys).. Abstract2012.skin_hedding_and_tissue_regeneration_in_african_spiny_mice_acomys..pdf

Evolutionary modification has produced a spectrum of animal defence traits to escape predation, including the ability to autotomize body parts to elude capture. After autotomy, the missing part is either replaced through regeneration (for example, in urodeles, lizards, arthropods and crustaceans) or permanently lost (such as in mammals). Although most autotomy involves the loss of appendages (legs, chelipeds, antennae or tails, for example), skin autotomy can occur in certain taxa of scincid and gekkonid lizards. Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing showed a propensity for skin to tear under very low tension and the absence of a fracture plane. After skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Notably, we found that regenerative capacity in Acomys was extended to ear holes, where the mice exhibited complete regeneration of hair follicles, sebaceous glands, dermis and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells) after limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through the assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of conventional model organisms, and suggests that mammals may retain a higher capacity for regeneration than was previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring.


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