Animal venoms are powerful, highly evolved chemical weapons for defense and predation. While veno... more Animal venoms are powerful, highly evolved chemical weapons for defense and predation. While venoms are used mainly to lethally antagonize heterospecifics (individuals of a different species), nonlethal envenomation of conspecifics (individuals of the same species) is occasionally observed. Both the venom and target specifications underlying these two forms of envenomation are still poorly understood. Here, we show a target-switching mechanism in centipede (Scolopendra subspinipes) venom. On the basis of this mechanism, a major toxin component [Ssm Spooky Toxin (SsTx)] in centipede venom inhibits the Shal channel in conspecifics but not in heterospecifics to cause short-term, recoverable, and nonlethal envenomation. This same toxin causes fatal heterospecific envenomation, for example, by switching its target to the Shaker channels in heterospecifics without inhibiting the Shaker channel of conspecific S. subspinipes individuals. These findings suggest that venom components exhibit ...
Angiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respirat... more Angiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to cause coronavirus disease 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody (EC50 ~16.6 nM) shows promising anti-viral effects in mouse model. Collectively,...
Hypercytokinemia is a critically fatal factor in COVID-19. However, underlying pathogenic mechani... more Hypercytokinemia is a critically fatal factor in COVID-19. However, underlying pathogenic mechanisms are unknown. Here we show that fibrinogen and leukotriene-A4 hydrolase (LTA4H), two of the most potent inflammatory contributors, are elevated by 67.7 and astonishing 227.7% in the plasma of patients infected by SARS-CoV-2 and admitted to intensive care unit in comparison with healthy control, respectively. Conversely, transferrin identified as a fibrinogen immobilizer in our recent work and Spink6 are down-regulated by 40.3 and 25.9%, respectively. Furthermore, we identify Spink6 as the first endogenous inhibitor of LTA4H, a pro-inflammatory enzyme catalyzing final and rating limited step in biosynthesis of leukotriene-B4 that is an extremely inflammatory mediator and a target to design superior anti-inflammatory drugs. Additionally, virus Spike protein is found to evoke LTA4H and fibrinogen expression in vivo. Collectively, these findings identify the imbalance between inflammatory...
Coumarins, naturally occurring phytochemicals, display a wide spectrum of biological activities b... more Coumarins, naturally occurring phytochemicals, display a wide spectrum of biological activities by acting on multiple targets. Herein, nine coumarins from the root of Toddalia asiatica were evaluated for activities related to pathogenesis of Alzheimer’s disease (AD). They were examined for acetylcholinesterase (AChE) and AChE- or self-induced amyloid beta (Aβ) aggregation inhibitory activities, as well as neuroprotection against H2O2- and Aβ1–42-induced human neuroblastoma SH-SY5Y cell damage. Moreover, in order to understand the mechanism, the binding interactions between coumarins and their targets: (i) AChE and (ii) Aβ1–42 peptide were investigated in silico. All coumarins exhibited mild to moderate AChE and self-induced Aβ aggregation inhibitory actions. In addition, the coumarins substituted with the long alkyl chain at position 6 or 8 illustrated ability to inhibit AChE-induced Aβ aggregation, resulting from their dual binding site at catalytic anionic site and peripheral acti...
Accidental contact with caterpillar bristles causes local symptoms such as severe pain, intense h... more Accidental contact with caterpillar bristles causes local symptoms such as severe pain, intense heat, edema, erythema, and pruritus. However, there is little functional evidence to indicate a potential mechanism. In this study, we analyzed the biological characteristics of the crude venom from the larval stage of Latoia consocia living in South-West China. Intraplantar injection of the venom into the hind paws of mice induced severe acute pain behaviors in wild type (WT) mice; the responses were much reduced in TRPV1-deficit (TRPV1 KO) mice. The TRPV1-specific inhibitor, capsazepine, significantly attenuated the pain behaviors. Furthermore, the crude venom evoked strong calcium signals in the dorsal root ganglion (DRG) neurons of WT mice but not those of TRPV1 KO mice. Among the pain-related ion channels we tested, the crude venom only activated the TRPV1 channel. To better understand the venom components, we analyzed the transcriptome of the L. consocia sebaceous gland region. Our ...
Slender leaf (Crotalaria spp) is among the indigenous and underutilized vegetables in Kenya whose... more Slender leaf (Crotalaria spp) is among the indigenous and underutilized vegetables in Kenya whose production is limited to the Western and Coastal regions of the country. For a long time, this crop has been neglected in terms of research and genetic improvement. There is therefore scanty information on its morphological diversity and agronomic performance, hence the need for this study. Field experiments were carried out for two seasons in October to December 2018 and March to May 2019. The experiments were laid out in Randomized Complete Block Design with 29 accessions and replicated three times. Both qualitative and quantitative data were recorded from the accessions based on the Crotalaria descriptors. Quantitative data were subjected to analysis of variance using XLSTAT Version 2019, and accession means were separated using Student’s Newman Keuls test at 95% level of confidence. Both qualitative and quantitative data were subjected to multivariate cluster analysis, and a dendrog...
MMWR. Morbidity and mortality weekly report, Jan 10, 2017
The collection, analysis, and use of data to measure and improve immunization program performance... more The collection, analysis, and use of data to measure and improve immunization program performance are priorities for the World Health Organization (WHO), global partners, and national immunization programs (NIPs). High quality data are essential for evidence-based decision-making to support successful NIPs. Consistent recording and reporting practices, optimal access to and use of health information systems, and rigorous interpretation and use of data for decision-making are characteristics of high-quality immunization information systems. In 2015 and 2016, immunization information system assessments (IISAs) were conducted in Kenya and Ghana using a new WHO and CDC assessment methodology designed to identify root causes of immunization data quality problems and facilitate development of plans for improvement. Data quality challenges common to both countries included low confidence in facility-level target population data (Kenya = 50%, Ghana = 53%) and poor data concordance between c...
ABSTRACT Senna spectabilis is a small, rounded deciduous tree commonly found in the lower parts o... more ABSTRACT Senna spectabilis is a small, rounded deciduous tree commonly found in the lower parts of Eastern province of Kenya. The plant is known to treat dysentery, menstrual cramps, whooping coughs and diabetes mellitus among the natives of Mbeere in Kenya. The present study investigated the amounts of phytonutrients, phytochemicals, mineral elements and in vitro antioxidant capacity of the leaf and stem bark powders of S. spectabilis. HPLC-UV/VIS, standard phytochemical methods, energy dispersive X-Ray fluorescence system, and 1, 1-diphenyl-2-picrylhydrazyl methods were used. Significant levels of retinol, α-tocopherol, thiamine, nicotinamide, β-carotene, lycopene, and β-cryptoxanthin were found in both leaf and stem bark powders. The antioxidant activity was 63.36, and 28.12%, for the leaf and stem bark powders, respectively. The free radical scavenging activity for the stem bark and leaf powders was 90.95%, and 88.98%. Also important mineral elements were found. The study findings support the claimed efficacy in the management of various diseases among the natives.
Animal venoms are powerful, highly evolved chemical weapons for defense and predation. While veno... more Animal venoms are powerful, highly evolved chemical weapons for defense and predation. While venoms are used mainly to lethally antagonize heterospecifics (individuals of a different species), nonlethal envenomation of conspecifics (individuals of the same species) is occasionally observed. Both the venom and target specifications underlying these two forms of envenomation are still poorly understood. Here, we show a target-switching mechanism in centipede (Scolopendra subspinipes) venom. On the basis of this mechanism, a major toxin component [Ssm Spooky Toxin (SsTx)] in centipede venom inhibits the Shal channel in conspecifics but not in heterospecifics to cause short-term, recoverable, and nonlethal envenomation. This same toxin causes fatal heterospecific envenomation, for example, by switching its target to the Shaker channels in heterospecifics without inhibiting the Shaker channel of conspecific S. subspinipes individuals. These findings suggest that venom components exhibit ...
Angiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respirat... more Angiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to cause coronavirus disease 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody (EC50 ~16.6 nM) shows promising anti-viral effects in mouse model. Collectively,...
Hypercytokinemia is a critically fatal factor in COVID-19. However, underlying pathogenic mechani... more Hypercytokinemia is a critically fatal factor in COVID-19. However, underlying pathogenic mechanisms are unknown. Here we show that fibrinogen and leukotriene-A4 hydrolase (LTA4H), two of the most potent inflammatory contributors, are elevated by 67.7 and astonishing 227.7% in the plasma of patients infected by SARS-CoV-2 and admitted to intensive care unit in comparison with healthy control, respectively. Conversely, transferrin identified as a fibrinogen immobilizer in our recent work and Spink6 are down-regulated by 40.3 and 25.9%, respectively. Furthermore, we identify Spink6 as the first endogenous inhibitor of LTA4H, a pro-inflammatory enzyme catalyzing final and rating limited step in biosynthesis of leukotriene-B4 that is an extremely inflammatory mediator and a target to design superior anti-inflammatory drugs. Additionally, virus Spike protein is found to evoke LTA4H and fibrinogen expression in vivo. Collectively, these findings identify the imbalance between inflammatory...
Coumarins, naturally occurring phytochemicals, display a wide spectrum of biological activities b... more Coumarins, naturally occurring phytochemicals, display a wide spectrum of biological activities by acting on multiple targets. Herein, nine coumarins from the root of Toddalia asiatica were evaluated for activities related to pathogenesis of Alzheimer’s disease (AD). They were examined for acetylcholinesterase (AChE) and AChE- or self-induced amyloid beta (Aβ) aggregation inhibitory activities, as well as neuroprotection against H2O2- and Aβ1–42-induced human neuroblastoma SH-SY5Y cell damage. Moreover, in order to understand the mechanism, the binding interactions between coumarins and their targets: (i) AChE and (ii) Aβ1–42 peptide were investigated in silico. All coumarins exhibited mild to moderate AChE and self-induced Aβ aggregation inhibitory actions. In addition, the coumarins substituted with the long alkyl chain at position 6 or 8 illustrated ability to inhibit AChE-induced Aβ aggregation, resulting from their dual binding site at catalytic anionic site and peripheral acti...
Accidental contact with caterpillar bristles causes local symptoms such as severe pain, intense h... more Accidental contact with caterpillar bristles causes local symptoms such as severe pain, intense heat, edema, erythema, and pruritus. However, there is little functional evidence to indicate a potential mechanism. In this study, we analyzed the biological characteristics of the crude venom from the larval stage of Latoia consocia living in South-West China. Intraplantar injection of the venom into the hind paws of mice induced severe acute pain behaviors in wild type (WT) mice; the responses were much reduced in TRPV1-deficit (TRPV1 KO) mice. The TRPV1-specific inhibitor, capsazepine, significantly attenuated the pain behaviors. Furthermore, the crude venom evoked strong calcium signals in the dorsal root ganglion (DRG) neurons of WT mice but not those of TRPV1 KO mice. Among the pain-related ion channels we tested, the crude venom only activated the TRPV1 channel. To better understand the venom components, we analyzed the transcriptome of the L. consocia sebaceous gland region. Our ...
Slender leaf (Crotalaria spp) is among the indigenous and underutilized vegetables in Kenya whose... more Slender leaf (Crotalaria spp) is among the indigenous and underutilized vegetables in Kenya whose production is limited to the Western and Coastal regions of the country. For a long time, this crop has been neglected in terms of research and genetic improvement. There is therefore scanty information on its morphological diversity and agronomic performance, hence the need for this study. Field experiments were carried out for two seasons in October to December 2018 and March to May 2019. The experiments were laid out in Randomized Complete Block Design with 29 accessions and replicated three times. Both qualitative and quantitative data were recorded from the accessions based on the Crotalaria descriptors. Quantitative data were subjected to analysis of variance using XLSTAT Version 2019, and accession means were separated using Student’s Newman Keuls test at 95% level of confidence. Both qualitative and quantitative data were subjected to multivariate cluster analysis, and a dendrog...
MMWR. Morbidity and mortality weekly report, Jan 10, 2017
The collection, analysis, and use of data to measure and improve immunization program performance... more The collection, analysis, and use of data to measure and improve immunization program performance are priorities for the World Health Organization (WHO), global partners, and national immunization programs (NIPs). High quality data are essential for evidence-based decision-making to support successful NIPs. Consistent recording and reporting practices, optimal access to and use of health information systems, and rigorous interpretation and use of data for decision-making are characteristics of high-quality immunization information systems. In 2015 and 2016, immunization information system assessments (IISAs) were conducted in Kenya and Ghana using a new WHO and CDC assessment methodology designed to identify root causes of immunization data quality problems and facilitate development of plans for improvement. Data quality challenges common to both countries included low confidence in facility-level target population data (Kenya = 50%, Ghana = 53%) and poor data concordance between c...
ABSTRACT Senna spectabilis is a small, rounded deciduous tree commonly found in the lower parts o... more ABSTRACT Senna spectabilis is a small, rounded deciduous tree commonly found in the lower parts of Eastern province of Kenya. The plant is known to treat dysentery, menstrual cramps, whooping coughs and diabetes mellitus among the natives of Mbeere in Kenya. The present study investigated the amounts of phytonutrients, phytochemicals, mineral elements and in vitro antioxidant capacity of the leaf and stem bark powders of S. spectabilis. HPLC-UV/VIS, standard phytochemical methods, energy dispersive X-Ray fluorescence system, and 1, 1-diphenyl-2-picrylhydrazyl methods were used. Significant levels of retinol, α-tocopherol, thiamine, nicotinamide, β-carotene, lycopene, and β-cryptoxanthin were found in both leaf and stem bark powders. The antioxidant activity was 63.36, and 28.12%, for the leaf and stem bark powders, respectively. The free radical scavenging activity for the stem bark and leaf powders was 90.95%, and 88.98%. Also important mineral elements were found. The study findings support the claimed efficacy in the management of various diseases among the natives.
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Papers by peter kamau